Withdrawal of useful drugs from the market
- Bill Lyndon
- Aust Prescr 2003;26:99-102
- 1 June 2003
- DOI: 10.18773/austprescr.2003.035
In the last few years pharmaceutical companies have announced the discontinuation of useful drugs in several areas of medicine. These withdrawals included four important psychotropic drugs. Three were antidepressants (nortriptyline, desipramine, phenelzine) and the fourth was benztropine, an anticholinergic drug widely used to control the extra pyramidal effects of antipsychotic drugs. Although the antidepressants involved are not frequently used, clinicians do not consider them to be obsolete and these drugs continue to have an important role in the management of treatment-resistant depression. Indeed, for a small but important minority of patients they are the drug of choice because of intolerance of, or failure to respond to, other antidepressants. An appreciable number of patients have been successfully maintained free of illness for many years because of long-term use of these antidepressants.
Following the announcements that the drugs would be withdrawn the Royal Australian and New Zealand College of Psychiatrists worked with the Department of Health and Ageing, the Pharmaceutical Benefits Advisory Committee (PBAC) and the companies to try and have these drugs retained for use in Australia and New Zealand. This approach was successful for three of the four drugs - desipramine was discontinued worldwide and is no longer manufactured. Unfortunately, supplies of phenelzine were rapidly and unexpectedly exhausted, forcing many patients to change to another antidepressant. Regrettably some patients experienced withdrawal symptoms or had a recurrence of depression after many years of stability, and in some cases hospitalization was required. These adverse outcomes show that the pharmaceutical industry, government and the medical profession need to work together to deal with the issue of proposed drug withdrawals in order to ensure that important drugs are retained for use.
A company may decide to discontinue the supply of a drug for various reasons. New products coming to the market inevitably mean that some older drugs appear to become redundant. Companies may then be under economic pressure to discontinue older, less profitable drugs. The cost of supplying a subsidised drug may, over time, exceed the price set by the Pharmaceutical Benefits Scheme. Failure to reach agreement on a higher price may lead the company to withdraw the drug rather than to continue supplying it at a price which is less profitable. Some older drugs are difficult to manufacture and the cost of upgrading the process to meet increasingly stringent government standards for manufacturing may beuneconomic. Occasionally new data may reveal unexpected adverse reactions, leading to discontinuation for safety reasons. Mergers of pharmaceutical companies may also result in a decision to stop manufacturing some products.
No matter how justified a company's decision may be, the discontinuation of an important drug has major implications for patients. This is particularly so for drugs which are used long-term to prevent disease or maintain health. These drugs include antidepressants, antipsychotics, antihypertensives and drugs for diabetes. Having to change from long-term treatment to a new drug can be a long and difficult process. It involves a significant risk of losing control of the illness, withdrawal reactions, recurrences of the illness, new adverse effects, and drug interactions. Sometimes more than one alternative may need to be tried and hospitalisation may result. Pharmaceutical companies need to advise and fully inform doctors and patients about the process of changing treatment to try and avoid inappropriate actions. Medicolegal issues relating to duty of care and responsibility are clearly relevant and no doubt will surface in time, potentially affecting the companies, individual doctors, pharmacists, specialist colleges and government bodies.
Currently, when a company decides to discontinue a drug, there is no formal process in place to prevent these problems. Nor is it usual for a company to secure the ongoing supply of an essential drug, by arranging for another company to continue its production or distribution, before announcing the decision to withdraw the product. Often the notice given is much too short for all patients to be satisfactorily transferred to an alternative drug before supplies run out, a situation compounded by the inevitable stockpiling which follows the announcement. In some instances the drug supply can continue by finding a generic supplier or through further price negotiations, but this is a lengthy process during which the drug may become temporarily unavailable.
Clearly it is in the best interest of all parties, particularly patients, to develop a co-ordinated and systematic approach to the discontinuation of important drugs. The pharmaceutical industry needs to develop guidelines to follow whenever a drug is being considered for withdrawal, including the early notification of health professionals, their colleges, and other relevant organisations. This would provide the opportunity for the profession to make a case for the retention of essential drugs. Ideally, companies should then join in the process, with government, of securing an alternative supplier. The colleges and other professional organisations need to ensure that they can respond quickly and have an established process for participating with the companies and government in trying to retain the drug. If unsuccessful, the colleges and the company need to work together to ensure that individual patients can be transferred to alternative drugs safely and effectively before supplies run out. This requires a system of rapid communication with clinicians to disseminate information and advice about potentially complex management problems. With sufficient goodwill between the parties involved and with a common focus on patient welfare, significant improvement in the management of drug discontinuations should be achievable.
E-mail: [email protected]
Clinical Lecturer, Department of Psychological Medicine, University of Sydney, Sydney
Chairman, Committee for Psychotropic Drugs and Other Physical Treatments, Royal Australian and New Zealand College of Psychiatrists