Statins and ED drugs lead the way, and there are plenty more on the horizon.
Pfizer wants to transform its faded prescription blockbuster Lipitor (atorvastatin) into the first blockbuster over-the-counter (OTC) statin. Merck wants to re-energize Mevacor (lovastatin) as an OTC product. There are just two problems.
Dave WendlandOne is the FDA, which has already declined to approve an OTC version of Mevacor three times since 2000. The second is space can be found on crowded pharmacy shelves for an entirely new product category.
“The two biggest categories vying for OTC status right now are statins and erectile dysfunction drugs,” said David Wendland, vice president of market research consultants, Hamacher Resource Group. “I don’t have a crystal ball, but ED drugs are probably closer to OTC approval than statins. The massive OTC advertising campaigns behind all of the ED products from their initial approval set the stage for OTC status. The general acceptance of erectile dysfunction as a condition than can be self-monitored and self-treated really sets up movement toward OTC status.”
Under current regulations, drugs are either Rx or OTC. There is no middle ground such as the “pharmacist directed” classification used in the United Kingdom (U.K.). Zocor 10 mg (simvastatin; Merck) was switched from Rx to OTC by U.K. regulators in 2004. Zocor Heart-Pro (McNeil) was the first OTC version to market.
But in order to carry the OTC version, U.K. pharmacies had to put the product behind the pharmacy counter. It can be sold only after the pharmacist has talked with the patient and determined the individual’s 10-year risk for a major cardiovascular event.
Individuals at low risk are ineligible for the drug. Those at moderate risk, 10% to 15% over 10 years, can buy a 28-day supply. Those at higher risk must see a physician for evaluation and, presumably, a higher-dose, Rx-only statin. Zocor Heart-Pro was discontinued in 2010 as a result of low sales, although other OTC versions remain available.
California-based Pharmacists Planning Services Inc. has filed repeated citizen petitions with FDA to establish a similar class of pharmacist-controlled “behind-the-counter” drugs. The agency has consistently denied PPSI’s petitions. In March, 2015, FDA turned thumbs down on requests to reclassify Lipitor, Narcan (naloxone; Amphaster, Hospira), Chantix (varenicline; Pfizer), and Viagra (sildenafil; Pfizer) as BTC products.
“FDA has not, to date, created a regulatory framework for drugs to be sold ‘behind-the-counter’ and we decline to do so now,” wrote Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research.
Tom MenighanDeclining to create a third class of drugs does not mean the FDA is content with the status quo. In 2012, the agency announced the Nonprescription Safe-Use Regulatory Expansion (NSURE) Initiative. The goal is to improve patient access to a wider range of medications.
“The FDA is looking to make definitions of prescription and OTC less rigid, so that certain nonprescription medications could be available through what it is calling ‘conditions of safe use,’” said Tom Menighan, BS Pharm, MBA, executive vice president and CEO of the American Pharmacists Association. “The FDA says it is not creating a third class of drugs, but that it has the regulatory latitude to allow more pharmacist involvement in the safe use of certain medications. The agency is looking at a new paradigm of drug safety with greater flexibility that will benefit patients and public health.”
The NSURE paradigm is based on a continuum of average risk. At one end of the scale are OTC products judged to carry relatively low risk. At the other end are agents that would not be approved because of excessive risk compared to the potential benefits. High-risk drugs would continue to be subject to risk evaluation and mitigation strategies (REMS); lower-risk drugs would be Rx-only.
Fred MayerA new category would include Rx drugs that have what FDA is calling “conditions of safe use” that would allow Rx products to move to an OTC-like status. Conditions of safe use could include intervention by a pharmacist or other healthcare provider, use of innovative technologies to improve safety, labeling requirements for safe use, or some combination.
“The FDA says there are only two classes of drugs in the U.S., OTC and Rx,” said PPSI President Fred Mayer, who is also a member of Drug Topics’ editorial advisory board. “So where do you put drugs like pseudoephedrine, which are required by federal law to be sold behind the counter under direct pharmacist control? How about insulin and syringes, or smoking cessation products that can be sold by pharmacists with specialized training in California and other states? The FDA has been in denial about our de facto third class of BTC drugs for a decade. It’s time they admitted the obvious.”
FDA maintains that pharmacist oversight of pseudoephedrine products and other specific categories encompasses individual exceptions required by law, not elements of any third class of drugs. The agency may not even create a regulatory framework for NSURE, as this could be seen as creating a third class of drugs. The agency is suggesting that it would rather see novel ideas to create the desired conditions for safe use that can be folded into the existing nonprescription regulatory pathway.
“Considering switches within the existing framework allows manufacturers more opportunity to pursue switches now, rather than waiting for regulations,” said Theresa Michele, MD, chief of the Division of Nonprescription Drug Products.
There is no lack of candidates for an Rx-to-OTC switch. Statins and ED drugs are just the beginning, Wendland said. Migraine, osteoporosis, and sleep formulations are also ripe for switch applications.
And while statins do not fit into an existing OTC category for cardiovascular health, aids for sexual health, headache, bone health, and sleep are all ready for new products. Tamiflu (oseltamivir; Genentech) and EpiPen (epinephrine auto-injector; Mylan) are other prime candidates, suggested Daniel Hussar, PhD, Remington Professor of Pharmacy, Philadelphia College of Pharmacy.
“From the outside, it is difficult to tell which Rx-to-OTC switches will be approved first,” Wendland said. “But once FDA shifts its stance to approval in a particular class, things can move pretty quickly. Just look at allergy products, where they approved the entire class. Sleeping aids and other categories could be in a similar position.”
Where does that leave pharmacists? In a solid position.
Menighan noted that pharmacists are ideally situated to help ensure safe use for innovative switch ideas. They are already heavily involved in immunization, medication therapy management, chronic disease management, and other direct patient services.
Pharmacists are already trained to provide clinical interventions such as drug therapy initiation for hyperlipidemia, diabetes, hypertension, and other dangerous conditions that are often asymptomatic in the early stages, which are more amenable to management. And a growing roster of states is expanding the way they define scope of practice to encourage pharmacists to take a more direct role in patient management, especially in situations where patients have limited access to primary care providers.
“We promote consumer access and coverage for quality patient care services [by pharmacists],” Menighan said. “We see NSURE as a platform on which pharmacists are involving patients to help ensure safer and more effective use of medications. Statins, for example, are relatively safe drugs with years of experience in the Rx market. The concern is that people will self-treat and ignore the larger cardiovascular issues. That is the kind of situation where pharmacist counseling and pharmacist involvement can enhance safety and more appropriate use of what is clearly a safe and highly effective class of drugs.”
Wendland also sees NSURE as a potential boost for pharmacists. FDA is calling for intervention by a healthcare professional and/or technological solutions to help patients better understand the risks and rewards of OTC medications, he said. The reality is that no technology solutions have been shown to promote the kinds of conditions for safe use that pharmacists are already trained to provide.
“If the FDA is serious about reducing healthcare costs, serious about reducing burdens on the healthcare system, and serious about improving consumers’ ability to take responsibility for their own care, some of these chronic classes of drugs are going to have to come over the counter,” he said. “It is clear that [patients] are going to need professional guidance to ensure a safe and effective switch. The professional and technology path could be a viable option, while technology-only switches are further off.”