Switching prescription drugs to over the counter
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《英国医生杂志》
1 Tufts Center for the Study of Drug Development, Tufts University School of Medicine, 192 South Street, Suite 550, Boston MA 02111, USA
Correspondence to: J P Cohen joshua.cohen@tufts.edu
Appropriate self treatment is an important aspect of both the European and American healthcare systems, but what is really driving increased over the counter availability?
Introduction
Generally, a prescription drug becomes a candidate for over the counter availability if it is used for a non-chronic condition that is relatively easy to self diagnose and has low potential for harm from abuse under conditions of widespread availability. Statins do not fit this description. Much has been said about the UK Medicines and Healthcare Products Regulatory Agency's controversial decision in May 2004 to reclassify simvastatin 10 mg as an over the counter medicine. In a best case scenario, the switch will increase use of simvastatin by people at moderate risk of developing coronary heart disease, resulting in reduced risk. However, there have been no clinical trials of over the counter statins for primary prevention of heart disease.
Concern has been raised that the main motive behind the government's decision to allow simvastatin to be sold directly to the public is the potential reduction in NHS expenditure.1 Although it is conceivable that the agency expedited the switch to save NHS costs, this is unlikely to have been the main motive. Firstly, the drug sponsor, and not the agency, initiated the switch,2 suggesting a profit motive. Secondly, NHS cost savings will be limited because high risk patients will still be eligible for statins on prescription; the target market for over the counter simvastatin is people at moderate and low risk, who are currently ineligible for NHS prescription (A Lawrence, MHRA, personal communication).
More prescription drugs are likely to become available over the counter
Credit: TIM BOYLE/GETTY IMAGES
Omeprazole
Cost was also the main motive behind the switching of the antihistamine loratadine to over the counter status in the United States. In an unprecedented move, Well-Point, a US health insurer, petitioned the Food and Drug Administration to switch three antihistamines: loratadine, cetirizine, and fexofenadine while they were well within patent.5-7 On review, the FDA recommended the switch in 1998. However, the FDA's recommendations are not binding; each manufacturer has to voluntarily initiate a switch of its drug. So far, only loratadine has been made available over the counter, and this was done in response to expiry of its patent. After losing a protracted patent litigation in spring 2002, Schering-Plough expected generic loratadine to enter the market later that year. To expand the brand name's viability, the company applied to switch loratadine at its original prescription strength of 10 mg, which the FDA approved in November 2002.
As a parallel strategy, drug firms often launch follow-on drugs to replace an innovator drug whose patent is expiring. Schering-Plough received US approval for loratadine's follow-on (desloratadine) in 2001 and launched it in 2002, near the end of loratadine's patent. A similar pattern was seen with omeprazole and the follow-on esomeprazole. Esomeprazole was launched in 2001, and the manufacturer successfully applied for omeprazole's switch to over the counter availability in 2003.8 The FDA approved a 20 mg dose for over the counter omeprazole (double that in Sweden). Omeprazole 20 mg also remains available as a prescription drug for treatment of diseases that require diagnosis and supervision by a healthcare provider.
Effect of over the counter availability
The FDA has been reluctant to allow switches of certain classes of drugs, such as corticosteroids, that have passed through regulatory hurdles in the European Union and elsewhere. One reason for this may be that, in contrast to most European regulatory agencies, the FDA requires studies of patients' understanding of labelling for each drug switched. Another reason may be that drugs in the United States are available only on prescription or over the counter. In many other countries, including Sweden and the United Kingdom, some drugs are classified as behind the counter—that is, available only with the authorisation of a pharmacist. The lack of a behind the counter option in the United States may heighten safety concerns because over the counter drugs are available to the public without any kind of professional intermediary.
Regulatory changes are underway in the United States. The FDA is currently considering over the counter status for certain drugs for chronic conditions, such as statins. The agency hopes to increase annual switches by about 50%.9 Moreover, the FDA is exploring its legal authority to initiate switches of drugs it deems suitable, specifically targeting 5-10 unspecified drugs that are available over the counter in other countries but not the United States. It will rely partly on foreign data to support claims that patients understand the labelling.
As a sign of a regulatory shift, the FDA has withdrawn its officially stated objection to switching lipid lowering drugs.10 It is currently reviewing two rejected switch applications for the statins lovastatin and pravastatin. It may be looking at data from the United Kingdom on over the counter simvastatin to evaluate these applications. If one or more statins were to be made available over the counter, copayments of prescription alternatives would probably rise, as has happened with second generation antihistamines and proton pump inhibitors.
Future implications
OTC statins: a bad decision for public health. Lancet 2004;363: 1659.
Medicines and Healthcare Products Regulatory Agency. Consultation document: ARM 18 Request to reclassify a product from POM to P. London: MHRA, 2003. www.mca.gov.uk/inforesources/publications/arm18.doc (accessed 13 Sep 2004).
Cohen J. Switching omeprazole in Sweden and the US. Am J Ther 2003; 10370-6.
World Self Medication Industry. OTC ingredients table. www.wsmi.org/otc.htm (accessed 13 Sep 2004).
Cohen J, DiMasi J. Modeling a switch of loratadine from prescription to over-the-counter status. J Res Pharm Econ 2001;11: 43-54.
Wellpoint. Issue paper: FDA petition for prescription to over-the-counter switch for Claritin, Allegra, and Zyrtec. www.fda.gov/ohrms/dockets/dockets/98p0610/cp00001.pdf (accessed 8 Mar 2004).
US Food and Drug Administration, Center for Drug Evaluation and Research. Public hearing on OTC part 15. June 28, 2000. www.fda.gov/ohrms/dockets/dockets/00n1256/tr00001.rtf (accessed 8 Mar 2004).
Nonprescription Medicines Academy. Joint FDA advisory committee recommends approval of Prilosec (omeprazole) for OTC switch at full prescription strength. www.nmafaculty.org/news/prilosec.htm (accessed 5 Feb 2004).
US Food and Drug Administration. FY 2004 FDA budget in brief: promoting public health through patient, food, and consumer safety. www.fda.gov/oc/oms/ofm/budget/2004/BIB.htm (accessed 29 Jan 2004).
Bristol Myers Squibb. Advisory committee meeting briefing book: for the Rx-to-OTC switch of: NDA 21-198 Pravachol? (pravastatin sodium) 10mg tablets. www.fda.gov/ohrms/dockets/ac/00/backgrd/3622b2a_part1.pdf (accessed 30 Jan 2004).(Joshua P Cohen, senior research fellow1,)
Correspondence to: J P Cohen joshua.cohen@tufts.edu
Appropriate self treatment is an important aspect of both the European and American healthcare systems, but what is really driving increased over the counter availability?
Introduction
Generally, a prescription drug becomes a candidate for over the counter availability if it is used for a non-chronic condition that is relatively easy to self diagnose and has low potential for harm from abuse under conditions of widespread availability. Statins do not fit this description. Much has been said about the UK Medicines and Healthcare Products Regulatory Agency's controversial decision in May 2004 to reclassify simvastatin 10 mg as an over the counter medicine. In a best case scenario, the switch will increase use of simvastatin by people at moderate risk of developing coronary heart disease, resulting in reduced risk. However, there have been no clinical trials of over the counter statins for primary prevention of heart disease.
Concern has been raised that the main motive behind the government's decision to allow simvastatin to be sold directly to the public is the potential reduction in NHS expenditure.1 Although it is conceivable that the agency expedited the switch to save NHS costs, this is unlikely to have been the main motive. Firstly, the drug sponsor, and not the agency, initiated the switch,2 suggesting a profit motive. Secondly, NHS cost savings will be limited because high risk patients will still be eligible for statins on prescription; the target market for over the counter simvastatin is people at moderate and low risk, who are currently ineligible for NHS prescription (A Lawrence, MHRA, personal communication).
More prescription drugs are likely to become available over the counter
Credit: TIM BOYLE/GETTY IMAGES
Omeprazole
Cost was also the main motive behind the switching of the antihistamine loratadine to over the counter status in the United States. In an unprecedented move, Well-Point, a US health insurer, petitioned the Food and Drug Administration to switch three antihistamines: loratadine, cetirizine, and fexofenadine while they were well within patent.5-7 On review, the FDA recommended the switch in 1998. However, the FDA's recommendations are not binding; each manufacturer has to voluntarily initiate a switch of its drug. So far, only loratadine has been made available over the counter, and this was done in response to expiry of its patent. After losing a protracted patent litigation in spring 2002, Schering-Plough expected generic loratadine to enter the market later that year. To expand the brand name's viability, the company applied to switch loratadine at its original prescription strength of 10 mg, which the FDA approved in November 2002.
As a parallel strategy, drug firms often launch follow-on drugs to replace an innovator drug whose patent is expiring. Schering-Plough received US approval for loratadine's follow-on (desloratadine) in 2001 and launched it in 2002, near the end of loratadine's patent. A similar pattern was seen with omeprazole and the follow-on esomeprazole. Esomeprazole was launched in 2001, and the manufacturer successfully applied for omeprazole's switch to over the counter availability in 2003.8 The FDA approved a 20 mg dose for over the counter omeprazole (double that in Sweden). Omeprazole 20 mg also remains available as a prescription drug for treatment of diseases that require diagnosis and supervision by a healthcare provider.
Effect of over the counter availability
The FDA has been reluctant to allow switches of certain classes of drugs, such as corticosteroids, that have passed through regulatory hurdles in the European Union and elsewhere. One reason for this may be that, in contrast to most European regulatory agencies, the FDA requires studies of patients' understanding of labelling for each drug switched. Another reason may be that drugs in the United States are available only on prescription or over the counter. In many other countries, including Sweden and the United Kingdom, some drugs are classified as behind the counter—that is, available only with the authorisation of a pharmacist. The lack of a behind the counter option in the United States may heighten safety concerns because over the counter drugs are available to the public without any kind of professional intermediary.
Regulatory changes are underway in the United States. The FDA is currently considering over the counter status for certain drugs for chronic conditions, such as statins. The agency hopes to increase annual switches by about 50%.9 Moreover, the FDA is exploring its legal authority to initiate switches of drugs it deems suitable, specifically targeting 5-10 unspecified drugs that are available over the counter in other countries but not the United States. It will rely partly on foreign data to support claims that patients understand the labelling.
As a sign of a regulatory shift, the FDA has withdrawn its officially stated objection to switching lipid lowering drugs.10 It is currently reviewing two rejected switch applications for the statins lovastatin and pravastatin. It may be looking at data from the United Kingdom on over the counter simvastatin to evaluate these applications. If one or more statins were to be made available over the counter, copayments of prescription alternatives would probably rise, as has happened with second generation antihistamines and proton pump inhibitors.
Future implications
OTC statins: a bad decision for public health. Lancet 2004;363: 1659.
Medicines and Healthcare Products Regulatory Agency. Consultation document: ARM 18 Request to reclassify a product from POM to P. London: MHRA, 2003. www.mca.gov.uk/inforesources/publications/arm18.doc (accessed 13 Sep 2004).
Cohen J. Switching omeprazole in Sweden and the US. Am J Ther 2003; 10370-6.
World Self Medication Industry. OTC ingredients table. www.wsmi.org/otc.htm (accessed 13 Sep 2004).
Cohen J, DiMasi J. Modeling a switch of loratadine from prescription to over-the-counter status. J Res Pharm Econ 2001;11: 43-54.
Wellpoint. Issue paper: FDA petition for prescription to over-the-counter switch for Claritin, Allegra, and Zyrtec. www.fda.gov/ohrms/dockets/dockets/98p0610/cp00001.pdf (accessed 8 Mar 2004).
US Food and Drug Administration, Center for Drug Evaluation and Research. Public hearing on OTC part 15. June 28, 2000. www.fda.gov/ohrms/dockets/dockets/00n1256/tr00001.rtf (accessed 8 Mar 2004).
Nonprescription Medicines Academy. Joint FDA advisory committee recommends approval of Prilosec (omeprazole) for OTC switch at full prescription strength. www.nmafaculty.org/news/prilosec.htm (accessed 5 Feb 2004).
US Food and Drug Administration. FY 2004 FDA budget in brief: promoting public health through patient, food, and consumer safety. www.fda.gov/oc/oms/ofm/budget/2004/BIB.htm (accessed 29 Jan 2004).
Bristol Myers Squibb. Advisory committee meeting briefing book: for the Rx-to-OTC switch of: NDA 21-198 Pravachol? (pravastatin sodium) 10mg tablets. www.fda.gov/ohrms/dockets/ac/00/backgrd/3622b2a_part1.pdf (accessed 30 Jan 2004).(Joshua P Cohen, senior research fellow1,)