Food and Drug Interactions Could Reduce Effectiveness of Oral Chemotherapy

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Oral chemotherapy agents are associated with drug and food interactions that can significantly reduce the effectiveness of oral chemotherapy and possibly result in harm to patients, according to a study in the Journal of Oncology Practice. It is important therefore, according to the study’s authors, to evaluate patients’ diet and concurrent medications and provide education, monitoring, and, if necessary, alternative recommendations.

A team of pharmacists led by Eve M. Segal, PharmD, of Froedtert and the Medical College of Wisconsin in Milwaukee, systematically reviewed 58 oral chemotherapeutics using U.S. Food and Drug Administration–approved product labeling, primary literature, and tertiary databases.

“Our study of drug interactions revealed that the addition of an oral chemotherapeutic to an anticoagulant may have unpredictable effects on the international normalization ratio (INR),” the pharmacists reported. “Approximately 16 of the oral chemotherapeutics affected the absorption of coumarin-­derived anticoagulants, and prolongation of the QTc interval was remarkable in 14 agents.” 

Acid suppression medications, such as proton-pump inhibitors, were found to affect absorption rates for nine oral chemotherapeutic agents. Warnings to avoid proton-pump inhibitors were included on the package inserts for dasatinib (Sprycel), erlotinib (Tarceva), and ponatinib (Iclusig).

“Manufacturers of several other oral chemotherapeutics recommend that avoidance of [proton-pump inhibitors] be considered,” the authors added. Bosutinib (Bosulif) and nilotinib ­(Tasigna) “have demonstrated increased absorption with concomitant [proton-pump inhibitor] therapy,” the authors noted. In addition, “[proton-pump inhibitors] interact with methotrexate, resulting in a delayed elimination, and therefore have the potential to cause methotrexate toxicity.” Because “acid suppression with [proton-pump inhibitors] is a drawn-out process,” they noted, timing doses to avoid a drug interaction can be “a futile exercise.”

Many drug-food interactions were noted. ”For nine drugs, ingestion with food was recommended, whereas 20 required that they be taken on an empty stomach. The fat content of a patient’s meal was noted as important in the total absorption of four of those medications advised to be taken on an empty stomach. Three drugs were noted to have interactions with calcium-containing foods or supplements, and nine drugs had pH-dependent absorption. Four of the oral chemotherapeutics noted significant quantities of lactose in the pills as inactive ingredients.” In addition, clinically significant or moderate interactions with grapefruit were noted for 19 drugs.

“Food interactions can be difficult to manage for patients receiving oral chemotherapy because of the lifestyle changes they might require, even if changes apply only to daily regimens, one meal a day, or time of day medication is taken. Changes in lifestyle can adversely affect the likelihood of adherence,” the pharmacists stated.

“It is imperative that health care providers monitor patients for potential food-drug and drug-drug interactions to avoid a loss in efficacy or increased risk of toxicity from oral chemotherapy,” the researchers concluded. ■

Segal, EM, et al: J Oncol Pract. April 22, 2014 (early release online).