Drug combinations - ? Polypill The young physician starts life with 20 drugs for each disease, and the old physician ends life with one drug for 20 diseases -William Osler Drugs must often be prescribed together for the same, related or different indications. Such will always risk interactions, in particular re competition for uptake/actions in the target organ/tissues and for elimination from the body.

Along with the desired clinical benefit, prescribed drugs necessarily cause a variety of unintended effects, some of which may impair quality of life, cause harms, or prove fatal. The risk of all of these effects naturally increases with dose. Higher doses are inevitably less safe and should be specifically warranted, e.g. with (all) steroids. Reduction of significant symptoms, like shortness of breath, angina or pain are obviously important goals. However, symptoms relief is rarely complete before significant toxicities emerge. In prevention, much is made of the ‘control’ of surrogate measures like cholesterol and glucose concentrations or blood pressure levels. However, increasing data from large clinical trials clarifies which drugs and doses are necessary with respect to the major clinical outcomes, in particular mortality.