Monitoring the safety of over the counter drugs

We need a better way than spontaneous reports

Last year the Food and Drug Administration in the United States recommended that phenylpropanolamine be removed from non-prescription and prescription medicines and that pharmaceutical companies voluntarily discontinue products containing phenylpropanolamine. This was in response to a case-control study by the Yale haemorrhagic stroke project investigators designed to determine the risk of haemorrhagic stroke in people exposed to phenylpropanolamine.1 Though this action was not followed in the United Kingdom, because the market conditions for phenylpropanolamine are different, the findings of the haemorrhagic stroke project highlight the need for continued monitoring of the safety of non-prescription medicines.

In the United States formulations of phenylpropanolamine contain up to 150 mg of a racemic mixture of two enantiomers of (±)-norephedrine,2 and withdrawal of appetite suppressants and cough and cold preparations containing phenylpropanolamine may well have been an appropriate response to the haemorrhagic stroke project data. In Europe the licensed maximum daily dose in non-prescription cough and cold remedies is lower (100 mg), and appetite suppressants containing phenylpropanolamine are not available in the United Kingdom. The UK's Committee on Safety of Medicines reviewed the data but concluded that products containing phenylpropanolamine did not need to be withdrawn.3 It considered that risk factors for haemorrhagic stroke were well known,4 and patient information leaflets for products containing phenylpropanolamine clearly state that they should not be used by people with high blood pressure, hyperthyroidism, coronary heart disease, and other risk factors because of the drug's sympathomimetic effects.5

Non-prescription medicines are often perceived as safe by the consumer because they are freely available for self selection. The haemorrhagic stroke project results show, however, that over the counter products may be far from innocuous. The current emphasis in healthcare is to shift some responsibility on to the consumer through expansion of self medication.6 Over the counter products in the United Kingdom have either a pharmacy only authorisation, which requires supervision of sale by a pharmacist in a pharmacy, or may be licensed for general sale in non-pharmacy retail outlets. In Britain the introduction of national guidelines has encouraged applications for reclassification of drugs from prescription only, which require the direct involvement of a medical practitioner, to pharmacy status. With further such switches scheduled, an increased number of powerful medications are likely to become available over the counter. Evidence from observational studies suggests that such products are not always used in accordance with the manufacturers' recommendations,7 so the use of over the counter drugs needs to be monitored and quantified.

In New Zealand pharmacists are actively encouraged to report adverse drug reactions involving prescribed or over the counter medicines to the Center for Adverse Reactions to Medicines. These spontaneous reports are followed up by requests for further clinical details from the patient's general practitioner. In 1999 the yellow card scheme for reporting adverse effects in the United Kingdom was extended to community pharmacists. Notifications from pharmacists will increase the number of notifications of adverse drug reactions and may generate new safety signals. Collaboration between pharmacists and physicians may also improve reporting, 8 9 especially as many physicians receive little formal teaching about over the counter medicines. However, the limitations of spontaneous reporting are well recognised. The reasons for doctors under-reporting adverse drug reactions include fear of litigation, diffidence, and complacency,10 and pharmacists are likely to hampered by similar constraints.

Patient medication records are a requirement for professional standards of good practice for pharmacists. Although records of dispensed prescriptions are used in everyday practice to draw attention to suspected drug interactions and adverse reactions, it is rare for pharmacists to record details of over the counter purchases. It may be time for that to change. In the interests of public health, pharmacists should be encouraged to use available computer facilities to record over the counter purchases when appropriate, with demographic details and the reason for purchase. In this way, as well as providing additional data for adverse drug reaction reporting, a further degree of control of the sale would be exercised to help ensure that the products are not used inappropriately.

Population based pharmacy databases could be used for modified prescription event monitoring11 studies. Pharmacy prescription event monitoring surveillance of selected pharmacy status drugs could be undertaken by sending questionnaires to pharmacists and asking them to fill in details from their database. Outcome data could be obtained from patients and their doctors. Telephone interviews for follow up have been used successfully to facilitate improved response.12 Though pharmacoepidemiological investigations such as cohort or case-control studies are feasible using cohorts of patients obtained from databases maintained by pharmacists, the practical difficulties need to be addressed in pilot studies.

The healthcare system must establish a practical yet scientifically robust method of surveillance of adverse reactions associated with over the counter medicines. The part of the pharmaceutical industry that deals with over the counter products seems commercially driven, and the funding of such pharmacovigilance is unlikely to come voluntarily from industry unless an element of statutory compulsion becomes a condition of the over the counter licence. As the queue of drugs waiting to gain over the counter status grows, now is the time to implement such controls.