From prescription-only to over-the-counter medicines ( PoM to P ): time for an intermediate category

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1 Published Online May 3, 2009 From prescription-only to over-the-counter medicines ( PoM to P ): time for an intermediate category Jeffrey K. Aronson * Department of Primary Health Care, University of Oxford, Rosemary Rue Building, Old Road Campus, Headington, Oxford OX3 7LF, UK Background: Increasing numbers of medicines are being made available over the counter in the UK, by purchase in a pharmacy or from other less wellregulated outlets. When this is allowed by the Licensing Authority, it is often subject to certain restrictions. However, some drugs that could usefully be converted from prescription-only medicines (PoM status) to over-the-counter sales in a pharmacy (P status) are not suitable for full over-the-counter status, even with restrictions; and in some cases restrictions vitiate the usefulness of the medicine. Areas of agreement: Drugs that can acceptably be switched from PoM status to P status include those that are used in the treatment of minor ailments or injuries, for health promotion or in palliative care. Areas of controversy: However, not all drugs that are being switched fall into these categories. Ready availability of antimicrobial drugs over the counter, one of which (azithromycin) has recently been switched, could encourage the emergence of resistant organisms. Drugs that are used for long-term treatment and lifestyle drugs are also controversial, particularly if their adverse effects are of potential concern. On the other hand, the availability of many drugs via the internet removes the ability of regulators to control the supply of such drugs. Accepted: April 8, 2009 *Correspondence to: J. K. Aronson, Department of Primary Health Care, University of Oxford, Rosemary Rue Building, Old Road Campus, Headington, Oxford OX3 7LF, UK. jeffrey.aronson@ clinpharm.ox.ac.uk A possible solution: A new category of purchase, Pharmacist Consultation and Supply, with built-in safeguards, could improve the availability of some medicines under more careful control than is currently available for overthe-counter medicines. Keywords: prescription-only medicines/pharmacy-only medicines/over-thecounter medicines/sildenafil/viagra/simvastatin British Medical Bulletin 2009; 90: DOI: /bmb/ldp015 & The Author Published by Oxford University Press. All rights reserved. For permissions, please journals.permissions@oxfordjournals.org

2 J. K. Aronson There are three legitimate ways of obtaining licensed medicines in the UK, defined in the 1968 Medicines Act. PoM: prescription-only medicines from qualified prescribers (doctors, dentists, nurse or pharmacist independent prescribers, or supplementary prescribers). P: pharmacy-only medicines, obtained without a prescription (colloquially, over the counter ) from, or under the supervision of, a qualified pharmacist. GSL: general sales list medicines, obtained without a prescription from, for example, a pharmacy or a supermarket. P and GSL medicines can also be prescribed in the usual way. Most medicines are restricted to prescription-only status, but in recent years, in political response to a perceived public demand for readier access to medicines, 1 increasing numbers of medicines have been reclassified (or switched ) from PoM to P. Examples have included omeprazole and simvastatin, both of which were switched in 2004, 2,3 and emergency contraception with levonorgestrel, which became available over the counter in Switches from P to GSL have also occurred. Before reclassification from PoM to P can occur, the Licensing Authority must be satisfied that it would be safe for the medicine to be supplied without a prescription. 5 A medicine may not be switched if it meets any of the following criteria, laid down in section 58A of the Medicines Act for a prescription-only medicine: it is likely to present a direct or indirect danger to human health, even when used correctly, if used without the supervision of a doctor; or is frequently and to a very wide extent used incorrectly, and as a result is likely to present a direct or indirect danger to human health; or contains substances or preparations of substances of which the activity requires, or the adverse effects require, further investigation; or is normally prescribed by a doctor for parenteral administration. However, there are positive criteria for switching, 6 criteria that are either necessary or desirable. 3 The necessary criteria are that: the patient either should be able to make the diagnosis or should know what the diagnosis is, based on an authoritative opinion; the treatment should be efficacious; the benefit-to-harm balance should be favourable. Additional, pragmatic reasons for switching are to make a medicine more readily and quickly available and to shift the cost from the public purse to the private British Medical Bulletin 2009;90

3 From PoM to P : time for an intermediate category Most P-category medicines are used in the treatment of minor ailments or injuries, for health promotion, or in palliative care, although the list is beginning to include medicines that are used for acute and chronic conditions that do not fall into these categories and may also be extended to lifestyle drugs, such as sildenafil for erectile dysfunction and orlistat for obesity. Black triangle drugs (recently licensed medicines whose adverse effects have not been extensively described) would not normally be considered as candidates for reclassification. In the face of new evidence, a P medicine can have its P status revoked, 7 as happened to terfenadine and astemizole, 8,9 when it was discovered that they could prolong the QT interval, with a risk of torsade de pointes, an effect that was enhanced by inhibition of their metabolism by grapefruit juice. 10 Even when a medicine is considered suitable for over-the-counter sales, those who advise the Licensing Authority may be reluctant to suggest granting P status, because of concerns about misuse, adverse drug effects and adverse drug drug interactions. When they do advise that a switch be granted, they will often recommend certain restrictions. 7 For example, both omeprazole and simvastatin (usual doses of mg/day) are supplied over the counter as tablets containing 10 mg. Omeprazole can be sold direct to adults over 18 years of age, only for the short-term relief of reflux-like symptoms, with a maximum daily dose of 20 mg, for a maximum of 4 weeks, in a pack of no more than 28 tablets; comparable restrictions apply to simvastatin. However, there is an important difference between these two drugs: as an over-the-counter drug omeprazole is used for short-term relief, whereas simvastatin is indicated for long-term prevention. Emergency contraception represents a third category one-off administration; in that case restrictions are not applied for the over-thecounter formulation both the indication and the dose are exactly the same as for the prescription formulation, and the two are identical in all respects (except for brand name and price). 11 Switching sildenafil In this issue of the British Medical Bulletin, Rubin and Wylie 12 ask whether sildenafil (Viagra w ) should be reclassified from PoM to P. They conclude that it should. Their arguments are sound, although they only tangentially allude to the fact that sildenafil can already easily be obtained over the counter, via the internet ( just Google buy Viagra ), by anyone who wants it for recreational purposes, 13 without any guarantee of quality, efficacy or safety, the three cornerstones of medicines regulation. In 2003 Viagra was fourth of the top 10 medicines British Medical Bulletin 2009;90 65

4 J. K. Aronson bought over the internet, the others being Xenical (orlistat for weight loss), Proscar (finasteride for benign prostatic hyperplasia), Propecia (finasteride for androgenetic alopecia in men), Uprima (sublingual apomorphine for erectile dysfunction), Reductil (sibutramine for appetite suppression), Zyban (bupropion for smoking cessation), Relenza (zanamivir for influenza), phentermine (for appetite suppression) and Meridia (sibutramine for appetite suppression). 14 This provides an argument for making it more readily available in reliable formulations. Other problematic medicines A possible solution But the current legislation poses a difficulty. The process of switching from PoM to P was made easier in 2002, and the P category is now overburdened by the different varieties of treatment that it includes. One-off or short-term treatments do not necessarily pose problems. A single tablet of levonorgestrel can be purchased for emergency contraception without the need for medical scrutiny, and the likelihood of an adverse effect is very small; limited supplies of sildenafil for erectile impotence could be comparable. Omeprazole and ranitidine, both available over the counter for the short-term relief of symptoms of heartburn, are similarly non-problematic, although one would hope that a pharmacist would advise any patient who buys them regularly to seek medical advice. However, the management of chronic problems is more difficult. Take, for example, irritable bowel syndrome, for which hyoscine butylbromide is licensed for over-the-counter purchase. The dosage is the same as the prescription dosage, but supply is limited to 3 days worth at full dosage (although patients can buy the drug over the internet). Furthermore, patients are advised not to use the drug unless their doctor has made the diagnosis of irritable bowel syndrome. 15 Why should such a medicine, for what is a chronic condition, be made available over the counter in this way? Presumably the manufacturer finds it profitable. This may be because many doctors doubt its efficacy (despite some evidence 16 ) and are likely to refuse to prescribe hyoscine butylbromide, while many patients, less than satisfied by the limited options their doctor offers them, will buy it over the counter and may gain relief. However, it may not be wise to allow a patient to keep on self-medicating, with a risk of missing a more serious diagnosis. 17 There is a case here for an intermediate category between PoM and P; let us call it PCS (Pharmacist Consultation and Supply). For medicines 66 British Medical Bulletin 2009;90

5 From PoM to P : time for an intermediate category in such a category, after diagnosis (usually by a doctor) the patient would buy a reasonable supply from a pharmacist, who would monitor their use of it and either repeat the order if they considered it appropriate or refer the patient back to the doctor. Some doctors will dislike the idea that a pharmacist might be given this kind of responsibility, but pharmacists already counsel patients, and the extra responsibility of dispensing a PCS product could encourage higher standards of pharmacy practice in initiating and monitoring therapy with selected medicines. Furthermore, safeguards could be introduced. For example, a pharmacist who supplies a PCS drug could be required to inform the patient s doctor; linked electronic records, if they become available, would add extra security, allowing the information to be transmitted automatically to the general practitioner (GP) and other pharmacists, thus controlling the extent of supply and facilitating research into outcomes. A PCS scheme would be comparable to the pharmacist-only scheme in Australia 18 and the restricted medicines scheme in New Zealand. 19 Recently, azithromycin has been accorded P status for treating infections with Chlamydia, the first oral antimicrobial drug to be so classified. There are serious concerns about the emergence of resistance organisms through overuse of antimicrobial drugs and there are reservations about this move. 20 Pharmacists are being required to undertake a diagnostic test through a central laboratory before selling azithromycin, 21 and this may be a sufficient safeguard. However, a PCS scheme would have been ideal for this drug and indication. Now consider how simvastatin for long-term prophylaxis of cardiovascular disease 22 might have been made available under such a scheme. Its over-the-counter formulation has been restricted to 10-mg tablets, too low a dose for a full beneficial effect, and pharmacists are required to ask a few simple questions about the patient s clinical condition before supplying it, without further monitoring of progress. Under a PCS classification, the pharmacist would be required to see the patient regularly, at least in the early stages, to titrate the dose in the absence of adverse effects (for example, muscle pains), and to warn about possible drug drug interactions; contrary to widespread opinion, one need not monitor the serum cholesterol concentration in these circumstances. 22,23 If necessary, the GP could be asked to advise. The availability of a PCS category intermediate between PoM and P would also allow newly switched drugs to be subjected to more careful scrutiny. Despite initial concerns, over-the-counter levonorgestrel for emergency contraception has established itself as safe and effective, and there has been no increase in the frequency of episodes of unprotected sex or any reduction in the use of other more reliable contraceptive methods as a result of its being available over the counter. 24 If British Medical Bulletin 2009;90 67

6 J. K. Aronson sildenafil were accorded PCS status, in time it would or would not prove itself in a similar fashion and could then be switched from PCS to P or from PCS to PoM. During this probationary period, the manufacturers would be required to provide the Licensing Authority with information about sales and post-marketing pharmacovigilance. In some cases (e.g. sumatriptan) the Medicines and Healthcare products Regulatory Agency already asks drug companies to carry out feasibility studies to troubleshoot potential problems before P status is granted. A private scheme whereby pharmacists can issue Viagra on a patient group direction is already available in some parts of the UK. 25 By all means let sildenafil be made available over the counter, but in small pack sizes, on a probationary basis, and under cover of a new category PCS medicines intermediate between PoM and P. Acknowledgements I am grateful to Robin Ferner and Nigel Baber for helpful comments on an early draft of this article. Conflict of interest J.K.A. is President of the British Pharmacological Society, but the views that he expresses here should not necessarily be taken to represent the views of other members of that Society. References 1 Speech by Jane Kennedy MP, Minister of State for Quality and Patient Safety, 23 November Self care and regulatory issues for the association of the European self-medication industry (AESGP) meeting. Available from Speecheslist/DH_ (accessed 9 February 2009). 2 Dhippayom T, Walker R (2006) Impact of the reclassification of omeprazole on the prescribing and sales of ulcer healing drugs. Pharm World Sci, 28, Aronson JK (2004) Over-the-counter medicines. Br J Clin Pharmacol, 58, Department of Health. Wider availability of emergency contraception. Available from (accessed 9 February 2009). 5 Medicines and Healthcare products Regulatory Agency. Legal status and reclassification. Available from Legalstatusandreclassification/index.htm (accessed 9 February 2009). 6 Fenichel RR (2004) Which drugs should be available over the counter? Br Med J 329, Ferner RE, Beard K (2008) Over the counter medicines: proceed with caution. Br Med J, 336, British Medical Bulletin 2009;90

7 From PoM to P : time for an intermediate category 8 Committee on Safety of Medicines, Medicines Control Agency (1997) Terfenadine: now only available on prescription. Curr Probl Pharmacovig, 23, 9. 9 Committee on Safety of Medicines, Medicines Control Agency (1999) Astemizole (Hismanal): only available on prescription. Curr Probl Pharmacovig, 25, Aronson JK (2001). Forbidden fruit. Nature Med, 7, Levonorgestrel. British National Formulary, Number 57. London: BMJ Group/RPS Publishing, March 2009, Rubin N, Wylie K (2009) Should sildenafil be available over the counter? Br Med Bull (in press). 13 Loe M (2004) The Rise of Viagra. How the Little Blue Pill Changed Sex in America. NY and London: New York University Press, House of Commons Committee of Public Accounts. Safety, quality, efficacy: regulating medicines in the UK. Twenty-sixth Report of Session Available from (accessed 9 February 2009). 15 Boehringer Ingelheim. Buscopan IBS Relief Summary of Product Characteristics. Available from (accessed 9 February 2009). 16 Ford AC, Talley NJ, Spiegel BM et al. (2008) Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. Br Med J, 337, a Kostopoulou O, Devereaux-Walsh C, Delaney BC (2009) Missing celiac disease in family medicine: the importance of hypothesis generation. Med Decis Making April 10, 2009 [Epub ahead of print]. 18 Emmerton L (2009) The third class of medications: sales and purchasing behavior are associated with pharmacist only and pharmacy medicine classifications in Australia. JAm Pharm Assoc, (2003), 49, Norris PT (2002) Purchasing restricted medicines in New Zealand pharmacies: results from a mystery shopper study. Pharm World Sci, 24, Hitchen L (2008) Switching antibiotics to pharmacy sale will increase resistance, doctors say. Br Med J, 337, a Royal Pharmaceutical Society of Great Britain. News Release, 6 November Society publishes azithromycin guidance. Available from (accessed 9 February 2009). 22 Wald NJ, Law MR (2003) A strategy to reduce cardiovascular disease by more than 80%. Br Med J, 326, Aronson JK (2004) Live long and prosper: a mass strategy for treating the factors associated with ischaemic heart disease and stroke. J Med Screen, 11, Marston C, Meltzer H, Majeed A (2005) Impact on contraceptive practice of making emergency hormonal contraception available over the counter in Great Britain: repeated cross sectional surveys. Br Med J, 331, Anonymous (2007) Boots launches private PGD service to supply Viagra. Pharm J, 278, 179. British Medical Bulletin 2009;90 69