Other Drug-Drug Interactions and Lifestyle-Drug Interactions

Food-Drug Interactions: Overview

The effect of food on the pharmacokinetics of an orally administered drug depends on the drug’s formulation and chemical properties, as well as gastrointestinal physiology and the type and quantity of food consumed.¹ Importantly, as food consumption delays gastric emptying, raises intestinal pH, increases hepatic blood flow and slows gastrointestinal transit, it can affect the pharmacokinetic behaviour of some orally administered drugs.¹

Food-drug interactions have four potential pharmacokinetic effects on the bioavailability of orally administered drugs: delayed, decreased, increased or unaffected absorption.¹

Food-drug interactions may occur with some kinase inhibitors, including an increase in the AUC with consumption of a high-fat meal (e.g. lapatinib).² However, some kinase inhibitors report no significant effect of food consumption on drug pharmacokinetics.²

Importance of Cytochrome P450 Enzymes in Lifestyle-Drug Interactions

As the activity of CYP enzymes in the gut wall is also a significant factor that alters the bioavailability of orally-administered drugs that are CYP3A4 substrates, food-drug interactions can also occur when an orally administered CYP3A4 substrate is co-administered with a food that is an inhibitor or inducer of intestinal CYP activity.¹ For example, grapefruit juice is a potent inhibitor of intestinal CYP3A4, thereby having the potential to increase the bioavailability of drugs that are CYP3A4 substrates when co-administered.¹ Also, the herbal medicine, St John’s Wort and smoking have each been reported to reduce erlotinib exposure by affecting CYP enzymes.³ A useful review article describing other foods and supplements that inhibit CYP enzymes can be found on the literature compilation page.

Approach to the Management of Food-Drug Interactions

Food-drug interactions are optimally managed by scheduling the oral administration of the drug with reference to meal timing (either before, with, or after a meal) to improve treatment outcomes.¹ Reporting of food-drug interactions is beyond the scope of this section, please refer to the kinase inhibitor prescribing information for more information on this topic.

References

1. Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer 2006; 6: 546-558.
2. Bardin C, Veal G, Paci A et al. Therapeutic drug monitoring in cancer--are we missing a trick? Eur J Cancer 2014; 50: 2005-2009.
3. Mathijssen RH, Sparreboom A, Verweij J. Determining the optimal dose in the development of anti-cancer agents. Nat Rev Clin Oncol 2014; 11: 272-281.