Opinion
VIEWPOINT
Joseph C. Pierson, MD University of Vermont College of Medicine, Burlington.
Corresponding Author: Joseph C. Pierson, MD, Dermatology Residency Program, University of Vermont College of Medicine, 111 Colchester Ave, Burlington, VT 05401 (joseph.pierson@uvm .edu). jamadermatology.com
Topical Prescription Contrition Shortly after I began prescribing certain topical medications in the early 1990s, I started to question the ritual. That universal thrill new clinicians experience when confidently knowing the diagnosis and its treatment was soon tempered by the realization that many patients had arrived already knowing both, and they resented a system that required the time, effort and expense of a formal appointment solely to procure what they deemed an effective but harmless remedy that they would then have to circle back and retrieve at a pharmacy they passed on the way to my office. Who could blame them? Encountering such patients 2 decades later, I grow more uncomfortable, perhaps a word not fully capturing the emotion. But that “sixth sense” finally prodded me to address the topic, fittingly through the sixth competency of the American College of Graduate Medical Education, “Systems-Based Practice”: “Residents must demonstrate an awareness of and responsiveness to the larger context and system of health care and the ability to effectively call on system resources to provide care that is of optimal value.” As residents being asked by a training program director to scrutinize established systemic processes of dubious value, they have every right to question why I have not addressed the ones I feel strongly about. Regarding my frustration with the multitude of topical prescriptiononly medications, one day that happened. There are many skin conditions that can be treated topically, but 3 common examples illustrate the impact that those medications available only by prescription have on US health care: treatment for head lice, scabies, and acne. Head lice are readily diagnosed by laypersons. The infestation occurs in approximately 10% of US schoolaged children, leading to frequent absences, and has an overall annual economic impact estimated at $1 billion.1 In most cases it is now resistant to standard over-thecounter (OTC) pediculicide treatments containing pyrethrins and pyrethroids (permethrin, 1%).1 In addition to “nit combing,” a variety of suboptimal occlusive home remedies are used. Fortunately, there is malathion, plus 3 newer topical products: ivermectin, spinosad (neither of which requires nit removal), and benzyl alcohol (a physical agent with low risk for future resistance). Unfortunately, despite being relatively harmless (with the exception of malathion’s flammability), each is available only by prescription at substantial cost: $152 for 2 oz, $257 for 4 oz, $219 for 4 oz, and $52 for 8 oz, respectively.2 The human scabies mite, whose triggering itch can have a significant impact on quality of life, infests approximately 1 million people in the United States each year.3 Permethrin, 5%, remains quite effective when properly applied, but the rationale for the prescriptiononly status of the higher concentration after its ap-
proval in this country a quarter of a century ago is unclear. What is clear is the tremendous difficulty in synchronizing the treatment of close contacts, which can span state boundaries and multiple pharmacies, often devolving into a regrettable game of “whack a mite.” Among other commercially available topical agents, crotamiton has lower cure rates, and lindane (which is banned in California) is rarely recommended owing to its toxicity. Oral ivermectin has proven efficacy but is not currently approved by the US Food and Drug Administration (FDA) for scabies or lice. Currently, easily obtainable effective treatments for these humbling ectoparasites are sorely lacking. Acne occurs in most Americans at some point in their lives. Benzoyl peroxide is the preferred OTC agent, but prescription topical retinoids (mainly tretinoin and adapalene) are also widely recommended as monotherapy or in combination regimens. The use of topical retinoids for this commonest of disorders involves all the requisite prescription formalities (to include prior authorization by some plans) and consumes enormous health care resources. National Ambulatory Medical Care Survey data from 1990 to 2004 showed office visits for topical retinoids, most of which were for acne, totaled 41.5 million.4 The necessity for many of those appointments could be questioned when considering that the main adverse effect of these 2 topical retinoids is similar to that of OTC benzoyl peroxide—skin irritation— and they share its FDA pregnancy category C status. Because oral retinoids are significantly teratogenic, FDA restrictions are in place for prescribing isotretinoin. However, 40 years after being released on the market, topical tretinoin has not shown an increased risk of embryopathy or other major birth defects.5 If theoretical pregnancy risk is the obstacle for topical tretinoin’s being available OTC, that should be weighed against proven pregnancy risks known to some currently available OTC medications, whose product labels bear appropriate warnings. There are myriad ramifications to pursuing a prescription-to-OTC switch for simple topical medications that may generate angst among clinicians. But history repeats itself, and the sky didn’t fall with the OTC release of cough and cold products, topical hydrocortisone, topical antifungals, nonsteroidal anti-inflammatory agents, first-generation antihistamines, topical minoxidil, second-generation antihistamines, proton pump inhibitors, or histamine 2 receptor blockers. The status quo regarding many topical prescription medications is ripe for questioning by vested stakeholders—foremost those with unique expertise in skin disease. But if a sea change is to occur, it should also be pushed along by the broader medical community who would likewise appreciate the minimal risks from certain topical prescriptions relative to OTC agents, such as JAMA Dermatology November 2014 Volume 150, Number 11
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Georgia User on 06/04/2015
1147
Opinion Viewpoint
aspirin, acetaminophen, or diphenhydramine. Surely, prescriptionto-OTC advocacy for topical dermatologics pales in boldness to the efforts by those who support OTC access for oral contraceptives. What are the costs savings for prescription-to OTC switches? In the case of second-generation antihistamines, over a decade ago it was estimated to be $4 billion annually.6 A more recent example is the oxybutynin transdermal patch treatment for overactive bladder in women, whose prescription-to-OTC cost plummeted from $320 to $29.7 It would be naïve not to mention the enormity of regulatory challenges involved in these conversions and the obvious economic implications for pharmaceutical companies amid patent expirations and generic competition. Prescription-to-OTC switches cost millions of dollars spent over a multiyear FDA procedural gauntlet, but must the path be so difficult? Consider a paradigm shift whereby all new topical agents considered for FDA approval be targeted for OTC usage, and that prescription-only status be designated by exception only, that is, those with clinically significant adverse effect profiles, agents ARTICLE INFORMATION
2. Ivermectin (Sklice) topical lotion for head lice. Med Lett Drugs Ther. 2012;54(1396):61-63.
Published Online: August 13, 2014. doi:10.1001/jamadermatol.2014.1298. Conflict of Interest Disclosures: None reported. REFERENCES 1. Yoon KS, Previte DJ, Hodgdon HE, et al. Knockdown resistance allele frequencies in North American head louse (Anoplura: Pediculidae) populations. J Med Entomol. 2014;51(2):450-457.
1148
used for the treatment of rare or complex conditions, or antiinfectives whose risk to benefit ratio for the potential development of resistant strains in the community is deemed too high. In addition, a separate fast-tracking of topical prescription-to-OTC switches should be created. From a pharmaceutical industry perspective, after investing millions in research and development, they should hope for an appropriate financial return, but isn’t there always money to be made with a safe, effective and conveniently accessible remedy for any common ailment? As mere cogs in the wheel of our complex health care world, we must still take responsibility for our role in any systems-based practice that does not optimize value, and I know the exact moment I was inspired toward action. It was when I realized the sensation of prescribing a simple topical medication to an exasperated patient was the same one I felt upon seeing a resident’s disappointment after learning I’d never sought its change. There was no escaping one word. Embarrassment.
3. Markell EK, John DT, Krotoski WA. Markell and Voge’s Medical Parasitology. 9th ed. Philadelphia, PA: W. B. Saunders; 2006. 4. Balkrishnan R, Bhosle MJ, Camacho F, Fleischer AB, Feldman SR. Prescribing patterns for topical retinoids: analyses of 15 years of data from the national ambulatory medical care survey. J Dermatolog Treat. 2010;21(3):193-200.
5. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation, I: pregnancy. J Am Acad Dermatol. 2014; 70(3):e1-e14. 6. Sullivan PW, Follin SL, Nichol MB. Transitioning the second-generation antihistamines to over-the-counter status: a cost-effectiveness analysis. Med Care. 2003;41(12):1382-1395. 7. Oxytrol OTC. Med Lett Drugs Ther. 2013; 55(1425):76.
JAMA Dermatology November 2014 Volume 150, Number 11
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Georgia User on 06/04/2015
jamadermatology.com
VIEWPOINT
Joseph C. Pierson, MD University of Vermont College of Medicine, Burlington.
Corresponding Author: Joseph C. Pierson, MD, Dermatology Residency Program, University of Vermont College of Medicine, 111 Colchester Ave, Burlington, VT 05401 (joseph.pierson@uvm .edu). jamadermatology.com
Topical Prescription Contrition Shortly after I began prescribing certain topical medications in the early 1990s, I started to question the ritual. That universal thrill new clinicians experience when confidently knowing the diagnosis and its treatment was soon tempered by the realization that many patients had arrived already knowing both, and they resented a system that required the time, effort and expense of a formal appointment solely to procure what they deemed an effective but harmless remedy that they would then have to circle back and retrieve at a pharmacy they passed on the way to my office. Who could blame them? Encountering such patients 2 decades later, I grow more uncomfortable, perhaps a word not fully capturing the emotion. But that “sixth sense” finally prodded me to address the topic, fittingly through the sixth competency of the American College of Graduate Medical Education, “Systems-Based Practice”: “Residents must demonstrate an awareness of and responsiveness to the larger context and system of health care and the ability to effectively call on system resources to provide care that is of optimal value.” As residents being asked by a training program director to scrutinize established systemic processes of dubious value, they have every right to question why I have not addressed the ones I feel strongly about. Regarding my frustration with the multitude of topical prescriptiononly medications, one day that happened. There are many skin conditions that can be treated topically, but 3 common examples illustrate the impact that those medications available only by prescription have on US health care: treatment for head lice, scabies, and acne. Head lice are readily diagnosed by laypersons. The infestation occurs in approximately 10% of US schoolaged children, leading to frequent absences, and has an overall annual economic impact estimated at $1 billion.1 In most cases it is now resistant to standard over-thecounter (OTC) pediculicide treatments containing pyrethrins and pyrethroids (permethrin, 1%).1 In addition to “nit combing,” a variety of suboptimal occlusive home remedies are used. Fortunately, there is malathion, plus 3 newer topical products: ivermectin, spinosad (neither of which requires nit removal), and benzyl alcohol (a physical agent with low risk for future resistance). Unfortunately, despite being relatively harmless (with the exception of malathion’s flammability), each is available only by prescription at substantial cost: $152 for 2 oz, $257 for 4 oz, $219 for 4 oz, and $52 for 8 oz, respectively.2 The human scabies mite, whose triggering itch can have a significant impact on quality of life, infests approximately 1 million people in the United States each year.3 Permethrin, 5%, remains quite effective when properly applied, but the rationale for the prescriptiononly status of the higher concentration after its ap-
proval in this country a quarter of a century ago is unclear. What is clear is the tremendous difficulty in synchronizing the treatment of close contacts, which can span state boundaries and multiple pharmacies, often devolving into a regrettable game of “whack a mite.” Among other commercially available topical agents, crotamiton has lower cure rates, and lindane (which is banned in California) is rarely recommended owing to its toxicity. Oral ivermectin has proven efficacy but is not currently approved by the US Food and Drug Administration (FDA) for scabies or lice. Currently, easily obtainable effective treatments for these humbling ectoparasites are sorely lacking. Acne occurs in most Americans at some point in their lives. Benzoyl peroxide is the preferred OTC agent, but prescription topical retinoids (mainly tretinoin and adapalene) are also widely recommended as monotherapy or in combination regimens. The use of topical retinoids for this commonest of disorders involves all the requisite prescription formalities (to include prior authorization by some plans) and consumes enormous health care resources. National Ambulatory Medical Care Survey data from 1990 to 2004 showed office visits for topical retinoids, most of which were for acne, totaled 41.5 million.4 The necessity for many of those appointments could be questioned when considering that the main adverse effect of these 2 topical retinoids is similar to that of OTC benzoyl peroxide—skin irritation— and they share its FDA pregnancy category C status. Because oral retinoids are significantly teratogenic, FDA restrictions are in place for prescribing isotretinoin. However, 40 years after being released on the market, topical tretinoin has not shown an increased risk of embryopathy or other major birth defects.5 If theoretical pregnancy risk is the obstacle for topical tretinoin’s being available OTC, that should be weighed against proven pregnancy risks known to some currently available OTC medications, whose product labels bear appropriate warnings. There are myriad ramifications to pursuing a prescription-to-OTC switch for simple topical medications that may generate angst among clinicians. But history repeats itself, and the sky didn’t fall with the OTC release of cough and cold products, topical hydrocortisone, topical antifungals, nonsteroidal anti-inflammatory agents, first-generation antihistamines, topical minoxidil, second-generation antihistamines, proton pump inhibitors, or histamine 2 receptor blockers. The status quo regarding many topical prescription medications is ripe for questioning by vested stakeholders—foremost those with unique expertise in skin disease. But if a sea change is to occur, it should also be pushed along by the broader medical community who would likewise appreciate the minimal risks from certain topical prescriptions relative to OTC agents, such as JAMA Dermatology November 2014 Volume 150, Number 11
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Georgia User on 06/04/2015
1147
Opinion Viewpoint
aspirin, acetaminophen, or diphenhydramine. Surely, prescriptionto-OTC advocacy for topical dermatologics pales in boldness to the efforts by those who support OTC access for oral contraceptives. What are the costs savings for prescription-to OTC switches? In the case of second-generation antihistamines, over a decade ago it was estimated to be $4 billion annually.6 A more recent example is the oxybutynin transdermal patch treatment for overactive bladder in women, whose prescription-to-OTC cost plummeted from $320 to $29.7 It would be naïve not to mention the enormity of regulatory challenges involved in these conversions and the obvious economic implications for pharmaceutical companies amid patent expirations and generic competition. Prescription-to-OTC switches cost millions of dollars spent over a multiyear FDA procedural gauntlet, but must the path be so difficult? Consider a paradigm shift whereby all new topical agents considered for FDA approval be targeted for OTC usage, and that prescription-only status be designated by exception only, that is, those with clinically significant adverse effect profiles, agents ARTICLE INFORMATION
2. Ivermectin (Sklice) topical lotion for head lice. Med Lett Drugs Ther. 2012;54(1396):61-63.
Published Online: August 13, 2014. doi:10.1001/jamadermatol.2014.1298. Conflict of Interest Disclosures: None reported. REFERENCES 1. Yoon KS, Previte DJ, Hodgdon HE, et al. Knockdown resistance allele frequencies in North American head louse (Anoplura: Pediculidae) populations. J Med Entomol. 2014;51(2):450-457.
1148
used for the treatment of rare or complex conditions, or antiinfectives whose risk to benefit ratio for the potential development of resistant strains in the community is deemed too high. In addition, a separate fast-tracking of topical prescription-to-OTC switches should be created. From a pharmaceutical industry perspective, after investing millions in research and development, they should hope for an appropriate financial return, but isn’t there always money to be made with a safe, effective and conveniently accessible remedy for any common ailment? As mere cogs in the wheel of our complex health care world, we must still take responsibility for our role in any systems-based practice that does not optimize value, and I know the exact moment I was inspired toward action. It was when I realized the sensation of prescribing a simple topical medication to an exasperated patient was the same one I felt upon seeing a resident’s disappointment after learning I’d never sought its change. There was no escaping one word. Embarrassment.
3. Markell EK, John DT, Krotoski WA. Markell and Voge’s Medical Parasitology. 9th ed. Philadelphia, PA: W. B. Saunders; 2006. 4. Balkrishnan R, Bhosle MJ, Camacho F, Fleischer AB, Feldman SR. Prescribing patterns for topical retinoids: analyses of 15 years of data from the national ambulatory medical care survey. J Dermatolog Treat. 2010;21(3):193-200.
5. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation, I: pregnancy. J Am Acad Dermatol. 2014; 70(3):e1-e14. 6. Sullivan PW, Follin SL, Nichol MB. Transitioning the second-generation antihistamines to over-the-counter status: a cost-effectiveness analysis. Med Care. 2003;41(12):1382-1395. 7. Oxytrol OTC. Med Lett Drugs Ther. 2013; 55(1425):76.
JAMA Dermatology November 2014 Volume 150, Number 11
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Georgia User on 06/04/2015
jamadermatology.com
