Targeted cancer therapy: interactions with other medicines

Abstract

Targeted therapy drugs, mainly those within the signal transduction inhibitors, are used more chronically than cytotoxic drugs and are metabolised by cytochrome P450 isozymes so patients are at high risk of having drug-drug interactions (DDI). Not only this, as the majority of them are given orally, new drug-drug interactions concerning gastrointestinal absorption can occur (e.g., with proton pump inhibitors). DDI can lead to changed systemic exposure, resulting in variations in drug response of the co-administered. In addition, concomitant ingestion of dietary supplements could also alter systemic exposure of drugs, thus leading to adverse drug reactions or loss of efficacy. In this review, we give an overview of the current existing data of known or suspected DDI between targeted therapy and other medicines. A review of package inserts was performed to identify drug-drug interactions for all targeted antineoplastic agents. Tertiary databases such as Lexicomp, Drugs, Martindale, Facts and Comparisons, and AHFS Drug Information were also referenced. This study covered 40 targeted antineoplastic agents (28 signal transduction inhibitors, 9 monoclonal antibodies and 3 other drugs, 2 monoclonal antibody conjugates and 1 fusion protein). Most of targeted therapy drugs are major CYP3A4 substrates with P-gp playing an important role in disposition too. Thus, there is a very common thread here that these agents will likely be sensitive victims to strong CYP3A4/P-gp inhibitors and inducers. It is essential that health care providers monitor patients for potential DDI to avoid a loss in efficacy or risk of greater toxicity from targeted therapy.

Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use

“…Previous studies demonstrated that co-administration of PPIs decreased the area under the plasma concentration-time curve of Gefitinib, Erlotinib, Dasatinib, Nilotinib, Lapatinib, Pazopanib, Selumetinib, and Sorafenib (Smelick et al, 2013;Conde-Estevez, 2016).…”

Combination Therapy for Metastatic Melanoma: A Pharmacist’s Role, Drug Interactions & Complementary Alternative Therapies

“…Vemurafenib can also inhibit CYP2C9 (e.g., warfarin) and CYP2D6 (e.g., dextromethorphan). An alternative should be considered or the substrate should be avoided if it has a narrow therapeutic index [ 36 , 46 , 52 , 55 ].…”

“…Dabrafenib is considered to be a major substrate of CYP2C8 and CYP3A4. Drugs that are either strong inhibitors or inducers of CYP2C8 should not be used concomitantly with dabrafenib (see Table 4 ) [ 36 , 46 , 52 , 56 ]. Strong CYP3A4 inducers may decrease the serum concentration of dabrafenib and one should monitor therapy closely; strong CYP3A4 inhibitors should be avoided because the may cause increased serum concentration of dabrafenib and exacerbate toxicities [ 52 , 56 ].…”

Intestinal Absorption of Geniposide and Inhibition of Transporter-P-GP Across the Caco-2 Monolayer

“…The development of new drugs and the wide application of drugs and herbs resulted in the potential of drug-drug interaction (DDI) have been noticed [4] . Membrane transporters, such as P-glycoprotein (P-gp), as a major barriers limiting oral drug delivery, play a key role in DDI, which can affect oral bioavailability, regulate the absorption, distribution and excretion of a large number of foreign substances [5] . Therefore, P-gp-related interactions have important clinical impacts and it is critical to understand which drugs are inducers or inhibitors of P-gp to minimize or avoid adverse interactions.…”