Targeted cancer therapy: interactions with other medicines

Area of Science:

• Oncology
• Pharmacology
• Drug Interactions

Background:

• Targeted therapy drugs, particularly signal transduction inhibitors, are used chronically.
• Their metabolism via cytochrome P450 isozymes and oral administration routes increase the risk of drug-drug interactions (DDIs).
• Concomitant use of dietary supplements can also affect drug exposure, leading to adverse reactions or reduced efficacy.

Purpose of the Study:

• To provide an overview of known and suspected DDIs between targeted therapies and other medications.
• To identify DDIs for targeted antineoplastic agents by reviewing package inserts and tertiary databases.

Main Methods:

• A comprehensive review of package inserts for targeted antineoplastic agents was conducted.
• Tertiary databases including Lexicomp®, Drugs, Martindale, Facts and Comparisons®, and AHFS Drug Information were referenced.
• The study covered 40 targeted antineoplastic agents, including signal transduction inhibitors, monoclonal antibodies, and other drug types.

Main Results:

• Most targeted therapy drugs are major CYP3A4 substrates, with P-glycoprotein (P-gp) also playing a significant role in their disposition.
• These agents are highly susceptible to interactions with strong CYP3A4/P-gp inhibitors and inducers.
• The review identified numerous potential DDIs affecting systemic exposure and therapeutic outcomes.

Conclusions:

• Healthcare providers must actively monitor patients undergoing targeted therapy for potential DDIs.
• Proactive management of DDIs is crucial to avoid loss of efficacy or increased toxicity associated with targeted antineoplastic agents.