Phenylbutazone and Oxyphenbutazone (Hansard, 6 March 1984)

§ Mr. Kenneth Clarke

The Committee on Safety of Medicines — CSM — began a general review of the relative safety of all non-steroidal anti-inflammatory drugs used in the treatment of arthritis and other painful conditions early in 1983. At its meeting on 22 September 1983 the committee considered about 40 products containing the substances phenylbutazone and oxyphenbutazone. Licences for products containing the former drug are currently held by 15 companies. Only Geigy Pharmaceuticals Ltd., however, has licences for products containing oxyphenbutazone.

The CSM accepted that both drugs were efficacious and that, because of this, they were still widely prescribed by doctors. The committee also accepted that the serious risks attaching to their use were well known to doctors. Nevertheless, the development of a large number of other drugs in this class over the past 20 years with a relatively lower incidence of serious adverse reactions made a reassessment of their risk/benefit ratio essential. Having considered the evidence carefully, the CSM provisionally concluded that, with the exception of eye drops containing oxyphenbutazone where the risks were comparatively small, the licences of all the products should be revoked in the light of concern about the frequency and severity of toxic effects, particularly on the bone marrow, and because there were no overriding clinical benefits to outweigh these risks. The committee also considered whether the licences should be suspended by the licensing authority with immediate effect on grounds of safety but advised that such action would not be justified.

In accordance with the procedures laid down in the Medicines Act 1968 all the companies were then informed of the CSM's provisional advice and offered the opportunity to make representations to the Committee orally or in writing. Geigy Pharmaceuticals Ltd. and Approved Pharmaceutical Services Ltd. decided to make written representations to the CSM and the other companies agreed that Geigy Pharmaceuticals' representations should also be accepted as theirs.

Geigy Pharmaceuticals' representations were considered by the CSM at its meeting on 23 February this year. After a further review of all the evidence the 500W committee confirmed its advice in relation to products containing oxyphen butazone. As regards products containing phenylbutazone the CSM accepted that the drug probably offered unique benefits to a small group of patients suffering from ankylosing spondylitis—arthritis of the spine — who would normally be referred to hospital for treatment. It advised therefore that those products should continue to be licensed on condition that the licences were varied to restrict the indications for use to ankylosing spondylitis and to limit their supply to hospitals only. If the licences are restricted in these ways, the Committee proposes to review data on the prescribing of these products in about 12 months' time.

The companies concerned have been informed of the CSM's advice on all these products by the licensing authority. The statutory procedures provide an opportunity to make oral or written representations against that advice to the Medicines Commission. Companies have 28 days under the Medicines Act to reach a decision following formal notification of the CSM's advice. As these legal procedures would take some time to complete, I asked the committee for its views on whether the licensing authority should suspend the product licences immediately. It confirmed its previous view that on the evidence before it suspension would not be justified.

All the companies concerned have agreed to comply with the CSM's advice in respect of products containing phenylbutazone or to cease marketing them. Those that wish to continue to market these products are being asked to submit applications making the necessary variations to their licences. All stocks of these products are to be withdrawn from retail pharmacies. Discussions are taking place with companies on the timing of withdrawal in order to ensure that doctors and patients are enabled to change to alternative courses of treatment in an orderly way.

As regards products containing oxyphenbutazone, Geigy Pharmaceuticals has not yet decided whether to make representations to the Medicines Commission. I will take action on the licences for these products immediately the company agrees to the CSM's advice or I receive the Medicines Commission's advice if the company does decide to make representations to that body.