Behind-the-Counter Availability of Certain Drugs – A Report from the Public Meeting at the FDA

Maria Marzella Sulli, PharmD

On November 14, 2007, the FDA held a public meeting to collect opinions on whether there should be "behind-the-counter" availability of certain drugs. If you are interested in self-care and nonprescription medicines, you know that this is an issue that has been debated for many years, and has resurfaced recently following the approval of Plan B as a "pharmacist-only" nonprescription product.

I had the opportunity to attend the public meeting, and wanted to share my experience with colleagues who may be interested. I have gained tremendous insight into the processes that govern our practice as pharmacists and learned just how important it is to be aware and be involved. In over 10 years as a pharmacist actively involved in the profession through organizations and academia, I had no prior knowledge of the inner workings of the FDA and how the decisions that shape our everyday work life are made. Many pharmacists I have spoken to since the meeting have shared with me that they were unaware of how to have their voices heard on certain issues. Not knowing what to expect when we signed on to present at the Public Meeting, I am hoping the reader will be able to gain some insight into what happens and how they can become more involved in the process.

The meeting opened at 8 a.m. with brief introductions to the topic by the Deputy Commissioner for Policy of the FDA and the Deputy Director of CDER for the FDA. With the background information presented, the meeting moved on to the public forum portion. The first round of speakers represented various professional organizations. The pharmacy organizations included APhA, ASHP, NCPA, and ACCP and all spoke of the value of the pharmacist and the need for this important class of medications that could improve patient's access to needed medications in a timely manner. The American Medical Association also sent a representative, and their position on the issue was not as favorable, citing that the FDA would not have the authority to create a third class of medications, and that the meeting was unnecessary.

The second panel of presenters, of which I was included, represented various academic institutions, as well as the Consumer Healthcare Products Association (CHPA) and the National Association of Boards of Pharmacy (NABP). Speaking for the Institute of Public Health and Pharmacy, Dr. Stuart Capper extolled the value this third class of medications would have on public health. Our presentation from St. John's focused on the training and education of pharmacists, highlighting the ACPE Standards requirements for knowledge and skills relating to assisting self-treating patients and the tremendous amount of preparation pharmacy students get during their education that would prepare them to handle the demands of overseeing this class of medications. Closing that session, the CHPA, who represent nonprescription medicine manufacturers, voiced their opinion that the current regulations allow flexibility for the FDA and companies to provide different approaches in moving prescription to nonprescription status.

The rest of the day was full of various presenters from different organizations presenting viewpoints on whether they agreed or disagreed with the possible formation of the "behind-the-counter" class of medications. Most informative in my opinion, was the presentation from Ms. Brigitte Zirger of Health Canada who was invited to present the classification system Canada uses for their medications. In Canada, three "Schedules" of medication exist. Schedule I drugs require a prescription, Schedule II requires professional intervention from the pharmacist but do not require prescriptions, and Schedule III drugs are sold only in an area of the pharmacy that is under direct supervision of the pharmacist. For Schedule III drugs, the pharmacist is available, accessible, and approachable, but intervention is not required. Lastly, Canada also has an unscheduled category which would be equivalent to our over-the-counter products. No supervision or intervention is required, and patients are free to self-select. Adopting such a system in the US, would require the development of two new categories of medications, but in my eyes, would be ideal for both protection of the patient and freedom to choose.

Many questions remain on this issue. First and foremost is whether the FDA has the authority to develop a new class of medications or whether this will require Congressional action. Once this debate is settled, how medications will be allocated into the classes remains to be solved. From the presentations witnessed, it appears that a manufacturer would "apply" for the status they prefer, as was the case with Plan B. Once rejected from one class, they may consider reapplying for a different class. Now that the Plan B precedent has been set however, we may see other medications apply for similar classification regardless of any regulatory changes.

A third class of "pharmacist-only" medications is well overdue. In the end, what this class will be called or how the interactions between the pharmacist and patient will be handled, remain to be defined. It would serve our profession well to be actively involved in the process, and to voice our ability and willingness to talk with patients, evaluate need for therapy, and play an active role in the care of patients by documenting our interventions. Without this necessary element, I feel the third-class would be "wasted" and relegate pharmacists to simply checking patient identifications.

What the future holds for us remains uncertain. I truly believe we will see this happen in upcoming years, and hope pharmacists see this as an opportunity rather than a burden.

Cetirizine (ZYRTEC®) Available Over-the-Counter

Emily M. Ambizas, Pharm.D., CDM

More than 50 million Americans suffer from allergic disease. It is the sixth most common chronic disease in the United States. Allergic rhinitis (AR) affects approximately 40 million people, up to 30% of adults and 40% of children.^1-2 Although there is no cure for this condition, treatment modalities are aimed at controlling the symptoms of AR, including sneezing, rhinorrhea, pruritus, and nasal congestion.

Unlike many other diseases, AR is not life-threatening; however, it can greatly affect a person's quality of life, disrupting daily functioning and sleep.³ As an increasing number of patients become more actively engaged in their health care needs, they will more likely self-diagnose and treat their allergic rhinitis when presenting to their pharmacist. This provides opportunities for pharmacists to have a greater impact on patient care. When managing AR, there are three major areas of focus: environmental control, pharmacotherapy, and immunotherapy.² Recognizing the role of pharmacists in assisting with the management of AR, an evidence-based pharmacotherapy guideline has been developed by Allergic Rhinitis and its Impact on Asthma (ARIA) in conjunction with the World Health Organization (WHO) entitled "Management of Allergic Rhinitis Symptoms in the Pharmacy".⁴

Pharmacists should first assess the patient's presenting history and symptoms, determining whether self management or referral to a physician is appropriate. When selecting an appropriate medication regimen, the pharmacist must consider efficacy, safety, and cost. Categories of medications available without a prescription includes antihistamines, decongestants, mast-cell stabilizers, and combination products, which help to relieve the symptoms of AR.

Until 2002, the only antihistamines available without a prescription were the first generation antihistamines, brompheniramine, chlorpheniramine, dimenhydrinate, diphenhydramine, and doxylamine, which are associated with high rates of sedation as well as anticholinergic adverse effects. In addition, these agents commonly require frequent dosing, 3-4 times daily, making adherence difficult. In November 2002, the FDA approved the Rx-to-OTC Switch of loratadine (Claritin®), the first second-generation antihistamine available without a prescription. The second-generation antihistamines, when compared to their predecessors, are associated with much lower rates of sedation, often being referred to as the non-sedating antihistamines. The ARIA guidelines recommend the use of these agents over the older agents due to their lower incidence of adverse effects.⁴

Pharmacists and allergy sufferers now have another second generation agent to recommend or choose without the need of a prescription – cetirizine (ZYRTEC®). The FDA has approved all forms of certirizine to be available behind the counter or over-the-counter.⁵ It is indicated for the temporary relief of symptoms due to hay fever or other respiratory allergies such as runny nose, sneezing, itchy, watery eyes, itchy throat or nose in persons 2 years of age and older. Cetirizine HCl 5 mg/pseudoephedrine HCl 120 mg (ZYRTEC-D®), in addition to the above indications, is also approved to relieve nasal congestion and pressure, as well as reducing swelling of the nasal passages and restoring freer breathing through the nose in adults and children 12 years and older. Cetirizine also carries the indication for relief of itching due to hives in persons 6 years of age and older. Cetirizine chewable tablets and tablets are approved for adults and children six years of age and older. The syrup is approved for adults and children 2 years of age and older.⁵

When deciding which agent to recommend to a patient, numerous factors must be considered. Although both loratadine and cetirizine have been shown to be efficacious in relieving the symptoms of allergic rhinitis, cetirizine appears to be superior over loratadine when compared in head-to-head studies. In these studies, cetirizine demonstrated a quicker onset of action and greater improvement in symptom scores when compared to loratadine.^6-9 Both agents are well tolerated, although cetirizine is associated with a risk of sedation at recommended doses. Cetirizine may be considered a mildly sedating antihistamine when compared to other second generation agents. It has been shown that somnolence related to cetirizine use is dose related, occurring in 6% of subjects receiving placebo, 11% of subjects receiving cetirizine 5 mg and in 14% of patients receiving cetirizine 10 mg.⁶ When compared to loratadine, somnolence is more prevalent; however, subjects did not discontinue treatment because of this effect.^6-9

Cetirizine was to be marketed as two distinct products for each dosage form. One product carries the indication and directions for treating symptoms of hay fever and other respiratory allergies. The second product carries the indication and directions for the relief of itching due to hives.⁵ However, at the time of this writing, ZYRTEC® syrup is the only dosage form to be marketed as two distinct products: Children's Zyrtec Allergy Syrup and Children’'s ZYRTEC® Hives Relief Syrup.

The cost of cetirizine for over-the-counter sales is approximately $20 for a one month supply.¹⁰ Although this switch may affect how insurers treat other second-generation antihistamines (increasing co-payments and requiring prior authorizations), one hopes it will be cost-effective for the patient despite this barrier. Since loratadine switched to non-prescription status, it has been shown to be cost-effective for patients, insurers and society.¹¹

References

1. American Academy of Allergy, Asthma and Immunology. Allergic Disorders: Promoting Best Practices. http://www.theallergyreport.com/reportindex.html Accessed: December 10, 2007
2. Berger WE. Overview of allergic rhinitis. Ann Allergy Asthma Immunol. 2003;90(Suppl 3): 7-12.
3. Schatz M. A survey of the burden of allergic rhinitis in the USA. Allergy. 2007: 62 (Suppl 85): 9-16.
4. Management of Allergic Rhinitis Symptoms in the Pharmacy. Allergic Rhinitis and Its Impact on Asthma (ARIA). Available at: http://www.whiar.org. Accessed: December 18, 2007.
5. FDA. FDA Approves Zyrtec for Nonprescription Use in Adults and Children. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01750.html Accessed: December 10, 2007
6. Day JH, Briscoe M, Rafeiro E, et al. Comparative onset of action and symptom relief with cetirizine, loratadine, or placebo in an environmental exposure unit in subjects with season allergic rhinitis: confirmation of a test system. Ann Allergy Asthma Immunol. 2001; 87:474-81.
7. Meltzer EO, Weiler JM, Widlitz MD. Comparative outdoor study of the efficacy, onset and duration of action, safety of cetirizine, loratadine, and placebo for seasonal allergic rhinitis. J Allergy Clin Immunol. 1996;97:617-26.
8. Day JH, Briscoe MP, Clark RH, et al. Onset of action and efficacy of terfenadine, astemizole, cetirizine, and loratadine for the relief of symptoms of allergic rhinitis. Ann Allergy Asthma Immunol. 1997;79:163-72.
9. Day JH, Briscoe M, Widlitz MD. Cetirizine, loratadine, or placebo in subjects with seasonal allergic rhinitis: Effects after controlled ragweed pollen challenge in an environmental exposure unit. J Allergy Clin Immunol. 1998;101:638-45.
10. Available at www.drugstore.com. Accessed on August 25, 2008.
11. Sullivan PW. Switching prescription drugs to over the counter: consumers may benefit financially in examples from the US. BMJ. 2005;330(7496):904-5.