Oral anticancer agents as generators of relevant pharmacokinetic interactions.

INTRODUCTION

The goal of this paper is to review the impact of marketed oral anticancer agents on the pharmacokinetics of co-administered medications in humans focusing on clinically relevant interactions.

METHODS

We identified the oral anticancer agents marketed in the United States and in Europe as December 31, 2021. Based on prescription information and literature, we selected the agents that were moderate/strong inducers or inhibitors of pharmacokinetic human molecular determinants of pharmacological interest (enzymes, drug transporters) highlighting on clinically meaningful interactions (i.e., at least a 2-fold variation in exposure of the comedication, excepting 1.5 for digoxin).

RESULTS

As December 31, 2021, 125 marketed oral anticancer agents were identified. Based on a≥2-fold exposure change (≥ 1.5 for digoxin), 24 oral anticancer agents commercialised in the European Union and the United States are susceptible to generate clinically meaningful pharmacokinetic interactions with comedications. All are recent agents and most of them (19/24) are indicated in the treatment of solid tumours. In all, 32 interactions with human molecular kinetic determinants were found for the 24 agents. Most of the pharmacokinetic interactions (26/32) are driven through cytochrome P450 (CYP) inhibition or induction, CYP3A4 being the major contributor (15).

CONCLUSION

24 anticancer agents (20% of the oral market) have the potential to significantly interact with co-administered drugs. These potential pharmacokinetic interactions are likely to occur in the ambulatory setting in a polymedicated and aged population, needing to reinforce the vigilance of community pharmacists and health care providers (particularly in thoracic oncology and genitourinary cancer) with these sometimes rarely prescribed agents.