With OTC simvastatin, U.K.’s statin prescriptions down

The United States may not switch to over the counter simvastatin until necessary precautions are taken.

In August 2004, the United Kingdom, through its Medicines and Healthcare products Regulatory Agency, changed the status of simvastatin 10 mg from “prescription required” to “pharmacist directed.”

This decision was based primarily on the results of the Heart Protection Study (HPS), which tested simvastatin 40 mg vs. placebo, and suggested that statins should be provided to those with increased risk for heart disease or with documented vascular disease, regardless of cholesterol level.

Rhonda Cooper-DeHoff

The over-the-counter switch of simvastatin was the first time in the United Kingdom that a chronic prevention drug had been deregulated. Up to that point, only drugs for the treatment of acute, self-limiting illnesses were deregulated.

Drug requirements

To have simvastatin 10 mg, marketed as Zocor Heart-Pro (ZHP, Merck), available to customers, British pharmacies must be willing to comply with the stipulations laid out during the approval process. These include that ZHP can only be dispensed after an interview with a pharmacist who determines a person’s 10-year risk for a major cardiovascular event; only one 28-tablet pack can be dispensed at a time and information regarding lifestyle modification programs, including smoking cessation, healthy eating and weight loss and regular exercise, should be made available at the time of purchase. Also, anyone wishing to obtain ZHP would do so at their own out-of-pocket expense, as opposed to the prescription version, which would be available for a co-pay or without cost depending on the person’s status and national health coverage plan.

Only individuals determined to be at moderate risk (approximately 10% to 15% 10-year risk) are eligible to purchase ZHP. Those with lower risk are not eligible, and those at higher risk are required to be seen by a physician and obtain a prescription, presumably for a higher statin dose and other appropriate cardiovascular care.

At the time of OTC switch approval, it was concluded that for those at moderate risk for CHD, reducing LDL would reduce the risk for CHD, regardless of the starting cholesterol level. Therefore, there is no requirement for pharmacists to check initial cholesterol levels, although a pharmacy can offer cholesterol testing if it so chooses.

Prescriptions decrease

Kristian B. Kilion, MSc, and colleagues recently assessed statin prescriptions in the United Kingdom using prescription history data from the General Practice Research Database, which includes information on approximately 3.5 million people. In the first quarter of 2005, soon after ZHP became available, prescriptions for statins began to fall, and importantly, this fall was not limited to 10 mg statin drugs as would be expected.

There was a significant decrease in all statin prescriptions, and the authors concluded that some patients may be inappropriately switching to the lower dose OTC statin. Using statistical modeling, the authors predicted that more than 600,000 fewer statin prescriptions were issued during the second quarter of 2005 in the United Kingdom than would have been predicted by pre-OTC switch prescription rates.

What is lacking in this published report is information on the sales volume of ZHP. A telephone survey of 165 pharmacies in six different geographic regions conducted by U.K. pharmacist Andrew Morrison, in conjunction with the Department of Medicines Management at Keele University during April and May 2005 to assess ZHP sales volume, shed some light.

One hundred forty-one (86%) of the 165 pharmacies surveyed stocked ZHP. However, only 13 pharmacies (9%) had sold a total of 18 ZHP packs during the prior two-month period. Sales were independent of socioeconomic status of the region and urban or rural status. There were more requests for ZHP than sales, primarily due to requestors not satisfying the required cardiovascular risk level or not willing to pay for it out of pocket.

Although results from this telephone survey are limited and may not be representative of ZHP sales in the entire country, it seems unlikely that ZHP sales explain the decrease in statin prescriptions observed by Filion et al.

FDA review

In July 2000, the FDA reviewed applications for the OTC switch of lovastatin (Mevacor, Altocor) 10 mg and pravastatin (Pravachol, Bristol-Myers Squibb) 10 mg, and in January 2005, lovastatin 20 mg was reviewed.

In 2000, the Nonprescription Drugs Advisory Committee unanimously agreed that both statins at the 10 mg dose were clinically safe and effective for the target population. However, a majority of the panel members voted against approval primarily because they were not convinced that consumers would use the drugs appropriately in the OTC setting and that, as a result, consumers would not achieve the stated clinical benefits. Additionally, they were concerned that consumers would not correctly self-select based on their cholesterol levels and other risk factors.

During the 2005 review, the advisory committee again unanimously agreed that the proposed target population merited treatment with a statin and that lovastatin 20 mg was an effective dose. They agreed that assessment of liver function was not necessary at baseline or during treatment and that the risk of muscle toxicity was acceptable for an OTC drug within the target population.

However, the committee was concerned about the potential for use in women of child-bearing potential who might not know they are pregnant. Again, the committee expressed concern with the general population’s ability to correctly self-select and self-diagnose, and thus safely use, an OTC statin without guidance of a physician. Therefore, the committee again recommended against approval of lovastatin for OTC sale.

The FDA switch principles suggest that, for a drug to be eligible for OTC status, the drug should be safe and effective and have a label that is easily understood. The condition it is used for should be able to be self-diagnosed, and consumers should monitor the success of the therapy.

Other guidance includes consideration of whether the benefits outweigh the risks and the potential for misuse. Nevertheless, the advisory committees are only asked to consider safety, efficacy and the appropriateness of self-diagnosis and self-medication.

Until these issues can be adequately addressed for the statins, it is unlikely that we will be seeing an OTC switch in the United States anytime soon.

Rhonda Cooper-DeHoff, Pharm D, is Assistant Director of Clinical Programs and Research Assistant Professor in the Division of Cardiology at University of Florida College of Medicine, Gainesville. She is a member of the Today in Cardiology’s Editorial Board.

For more information:

• Filion KB, Delaney AC, Brophy JM, Ernst P, Suissa S. The impact of over-the-counter simvastatin on the number of statin prescriptions in the United Kingdom: A view from the General Practice Research Database. Pharmacoepidemiol Drug Saf. 2007;16:1-4.
• Personal communication with Andrew Morrison.