Pharmacological appraisal of fixed-dose combination medicines: discussion paper.

Combination medicines can offer advantages over single products and over multiple drug regimes; at present they account for about one-third of medicines used in general practice and one-fifth in hospital. The alleged disadvantages of such products are mostly theoretical or doctrinal, with the strongest being an objection to the fixed ratio of the ingredients. Nearly all medicines are a formulated mixture of several chemicals and a single active ingredient may be metabolized to a variety of substances with different therapeutic and toxic effects. Hence, the basis of this main objection must be to the fixed ratio of the properties of the multiple ingredients. However, most single drugs, as well as most physiological substances, induce a range of different actions in the body in fixed ratio. Homeostasis is achieved through multicomponent pathways and as such may have advantages in the quality of control compared with the use of any single effector; the same principle may apply pharmacologically in the long-term stabilization of functions such as blood pressure and blood sugar. Thus, discrimination against combination medicines per se on these pharmacological grounds is questionable and should not be allowed to hamper a potentially useful area of therapeutic research. Some recent combination products have provided notable advances in therapeutics and suggest that this could be extended in ways that would not involve the cost and lengthy development of new single-chemical entities.