Oral Anticancer Therapy: Management of Drug Interactions

Britny G. Rogala, PharmD; Margaret M. Charpentier, PharmD; Michelle K. Nguyen, PharmD; Kaitlin M. Landolf, PharmD; Lamya Hamad, RPh; Kelly M. Gaertner, PharmD

Disclosures

J Oncol Pract. 2019;15(2):81-90. 

In This Article

Abstract and Introduction

Abstract

Oral anticancer therapy is increasingly integrated into the care of patients with cancer. Recognition and management of drug-drug interactions (DDIs) is critical to providing efficacious and safe anticancer treatment. DDIs with QTc-prolonging agents, anticoagulants, enzyme inducers and inhibitors, antidepressants, and acid suppressants are commonly encountered with anticancer therapies. Here, we review frequently observed DDIs and outline literature-supported suggestions for their management.

Introduction

Oral anticancer therapies have become an integral part of hematology and oncology practice, gaining a strong presence in a wide range of treatment regimens, either as monotherapy or in combination with other anticancer medications. Though the concept of oral chemotherapy is not new, the past decade has experienced an increase in the approval and use of oral anticancer therapies.[1]

Over the past few years, the majority of new anticancer drugs approved by the US Food and Drug Administration have been oral formulations as opposed to intravenous.[2] This trend in increased use of oral anticancer therapies is responsible for altering the traditional hematology and oncology practice model, which has been based primarily on injectable treatments.[2]

Although prescription of oral anticancer therapies may provide a convenient and preferable option for appropriate patients, their use is associated with alternative challenges. In addition to potential issues such as insurance coverage, cost, time to obtain medication, and patient adherence, significant drug-drug interactions (DDIs) are more prevalent with oral anticancer medications than with injectable agents.[1,3] DDIs may occur via a variety of mechanisms. A pharmacokinetic interaction results when one drug affects the absorption, distribution, metabolism, or excretion of another.[4] This type of interaction most commonly involves factors affecting absorption or effects on the cytochrome P (CYP) 450 enzymes. When medications are administered intravenously, absorption issues are bypassed. Pharmacodynamic DDIs lead to an alteration of pharmacologic effect, which may be additive, synergistic, or antagonistic, and usually are a result of overlapping mechanisms of action or toxicities.[4,5] Pharmacokinetic interactions through the CYP enzyme pathway are typically studied in vitro as a part of the Food and Drug Administration approval process, whereas pharmacodynamic interactions are typically encountered during clinical trials when toxicities occur.

Tyrosine kinase inhibitors (TKIs) make up a significant portion of all oral anticancer therapies. As TKIs are only available in an oral formulation, issues with pharmacokinetic and pharmacodynamic drug interactions are common.[5] For example, most TKIs are CYP3A4 substrates; therefore, pharmacokinetic interactions are common, because exposure may be affected by inhibitors or inducers.[6] To further complicate matters, data regarding specific interactions or management may be limited, as DDI studies may be incomplete before drug approval is obtained. Often, in vitro data, preclinical animal studies, or small phase I trials may compose the extent of available pharmacokinetic information.

Oral drug delivery presents unique considerations, and an understanding of DDIs is crucial for the hematology and oncology practitioner. Important interactions with oral anticancer therapies may contribute to increased toxicity or reduced efficacy if not managed appropriately. Prescription of an oral anticancer therapy should occur after a thorough review of concomitant medications, to address any real or potential DDIs. Patients should also receive counseling on proper medication administration to ensure optimal absorption and minimize toxicity.

This review offers a comprehensive summary of common, significant DDIs and evidence-based management with various oral anticancer therapies, with an emphasis on QTc prolongation, bleeding, CYP3A4 inhibitors and inducers, antidepressants, and acid suppressants. The prescribing information for each medication discussed was reviewed and cross-referenced to tertiary databases such as Lexicomp (www.lexi.com; Wolters Kluwer, Hudson, OH) and the IBM MicroMedex Drug Interaction Checking tool (https://www-01.ibm.com/common/ssi/cgi-bin/ssialias?htmlfid5HPD12384USEN; IBM, Armonk, NY).

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