ABSTRACT
Combination drugs are drugs that contain two or more different pharmacological agents in one preparation. The dosage of the different ingredients is fixed; thus, the term fixed combination or fixed dose combination is common for this combination of drugs.1 Among the major advantages physicians claim for combination drugs are: improved effectiveness with a reduced adverse reaction profile, better patient compliance, better protection against drug abuse, and fewer direct costs. A summary of the various rationales for fixed combinations is shown in Table 5.1. Pharmacologists, however, routinely emphasize disadvantages like the lack of a well-proven synergistic beneficial action of the different ingredients, impossibility to dose the different active agents individually according to the patients' responses, and different half-lives of the two or more agents. Despite these differing views fixed combinations present in many countries a relevant share of the drug market. The purpose of this chapter is to outline regulatory, clinical-pharmacological, and methodological requirements for the assessment of the benefits and risks of combination drugs and to present appropriate clinical examples. We conclude with the problems of establishing the benefit/risk ratio.
