For a fixed dose combination, the pharmacokinetics of individual active substances should be well documented. In general, it is required to demonstrate that the individual components do not affect known pharmacokinetic patterns of individual substances.
If a pharmacokinetics interaction exists, it must be justified. Data of drug-drug interaction clinical study should be presented. Alternate evidence such as in vitro data, mechanistic models or well acceptable published reference scientific evidence that supports pharmacokinetic rationale are helpful.
Question on potential pharmacokinetic interactions in high-risk subgroups (elderly, renal failure or hepatic impairment patients) may be necessary to support the rational use with favorable benefit-risk.
