Fixed combination drug therapy

Abstract

Almost half of all marketed drugs are fixed combination preparations, yet the World Health Organization included only 7 in its list of 240 "essential' drugs. There has been little scientific study of these preparations but much emotion and rhetoric has been expended both for and against them. Potential advantages of fixed combination preparations include: increased compliance, synergy and increased efficacy, and reduced side effects and cost. Potential disadvantages include: inflexible fixed dose ratio, incompatible pharmacokinetics, increased toxicity, and physician and pharmacist ignorance of content. There are a few combinations of undisputed value such as oral contraceptives, levodopa with decarboxylase inhibitors, and pyrimethamine with sulphadoxine. In other cases fixed-dose combinations may have value in strictly specified circumstances, but are probably overprescribed. There is also widespread, unjustified use of combinations in over-the-counter preparations which may have unrecognised adverse effects. Combinations should only be used if each component is necessary for the desired effect and if the advantages outweigh the added risks of using 2 or more drugs. Before prescribing combination drugs, clinicians should always ask themselves a series of questions of which the most important is whether the patient needs each drug in a particular combination, or if 1 component alone would be adequate. In general, government regulatory bodies in "developed' countries are attempting to curb the use of combination drugs, but a more profitable approach might be to better educate doctors on both the advantages and disadvantages of fixed combination preparations leading to improved prescribing habits.