5 drug-food interactions to beware

By Naveed Saleh, MD, MS
Published June 29, 2020

Key Takeaways

The ideal drug not only results in permanent cure but is extremely specific in its actions, has the same effects in all patients, never interacts with food or drugs, is linearly potent, and is non-toxic at any concentration. Good luck finding that perfect drug!

Most drugs contain strong ingredients that interact with the body in a myriad of ways. Such interactions may yield either increased/decreased potency or totally new effects. Drug-drug interactions frequently come to mind, and more recently, there’s been increased focus on drug-herb interactions. But, drug-food interactions also contribute to drug bioavailability.

The most important drug-food interactions involve treatment failure due to decreased bioavailability in the sated state. These interactions result from chelation with food components. Moreover, gastric acid secretion can decrease or increase drug bioavailability.

With that in mind, be sure to consider these five drug-food interactions during prescription.

Carbamazapine and beverages

Carbamazepine was introduced in the 1960s and has long been standard therapy for partial seizures, generalized tonic-clonic seizures, bipolar disorder, and trigeminal neuralgia. Carbamazepine, however, interacts with several drugs, herbal products, and foodstuffs. Specifically, the drug’s metabolism is hepatic and it strongly triggers the CYP450 system. It also leads to autoinduction, which refers to a drug’s ability to induce enzymes that enhance its self-metabolism, thus leading to tolerance.

In a systematic review of the literature, published in Evidence-Based Complementary and Alternative Medicine, the authors cited several different types of beverages that don’t agree with carbamazepine:

  • Coca-Cola increased the oral bioavailability of carbamazepine, possibly due to enhanced dissolution of the drug due to the soft drink’s acidity levels

  • Alcohol increased oral bioavailability of carbamazepine by decreasing its metabolism in those dependent on alcohol, but it did not affect metabolism in those without alcohol misuse

  • Caffeine lowered the drug’s bioavailability as well as its antiepileptic efficacy in human studies

Mercaptopurine and milk

This purine analog is used to treat chronic myelogenous leukemia and acute lymphoblastic leukemia. Xanthine oxidase, which is found in high levels in cow’s milk, inactivates this drug. Specifically, this enzyme changes 6-mercaptopurine into 6-thioxanthine and 6-thiouric acid, which are both devoid of therapeutic activity. 

Both in vivo and in vitro studies have demonstrated that drinking cow’s milk while taking mercaptopurine decreases its bioavailability and may result in clinically significant interactions. Consequently, experts suggest refraining from drinking cow’s milk around the time of taking the drug. 

Acetaminophen and pectin 

Pectin is a setting agent used in jams and jellies. This soluble gelatinous polysaccharide naturally occurs in ripened fruits. Some research has indicated that ingestion of pectin interferes with the absorption of acetaminophen by unknown mechanisms. Similarly, many types of cruciferous vegetables, such as broccoli, cabbage, and Brussels sprouts, as well as carbohydrates, can also interfere with acetaminophen absorption.

Tamoxifen and sesame seeds

Phytoestrogen-rich soy and flaxseed are sometimes used by premenopausal breast cancer patients to treat adverse effects of tamoxifen. Indeed, lignan-rich flaxseed protects against breast cancer and boosts the efficacy of tamoxifen. However, sesame seeds—which are also a rich source of lignan—may not have the same effect, according to the results of a preclinical study involving a mouse model. 

“This study determined the interactive effects of lignan-rich sesame seed (SS) and TAM [tamoxifen] on estrogen-responsive MCF-7 breast tumor growth and bone health in ovariectomized athymic mice under premenopausal-simulated conditions,” the authors wrote.

“Palpable tumor data, adjusted for body weight, showed that SS does not inhibit MCF-7 tumor growth and tends to negate the tumor inhibitory effect of TAM by increasing cell proliferation and reducing apoptosis. SS alone and combined with TAM enhanced femur biomechanical strength but caused no differences in bone mineral content or bone mineral density in either the femur or lumbar vertebrae. SS is not protective and interacts adversely with TAM in MCF-7 breast tumors but induces beneficial effects on bone both alone and when combined with TAM,” they concluded.

Esomeprazole and fatty foods

The proton-pump inhibitor esomeprazole is the S-isomer of racemate omeprazole and used for acid-related disorders, such as gastroesophageal reflux disease and erosive esophagitis.

Although researchers have known that meals with a high fat content slow gastric emptying—which can result in decreased absorption of the drug—they haven’t known how the timing of food impacts the drug’s effect. So, for this novel study, the researchers examined the pharmacokinetics of esomeprazole before ingestion of a high-fat meal compared with that of fasting. 

This open-label, randomized, crossover study of 44 healthy adults entailed two 5-day dosing periods of esomeprazole 40 mg per day. Participants either took esomeprazole 15 minutes before a high-fat meal (fed) or 4 hours before a non-high-fat meal (fasting). The 15‐minute interval between taking esomeprazole and eating approximated the real‐life habits of patients, the authors noted.

They found that taking the PPI within 15 minutes of eating a high-fat, high-calorie meal decreased systemic drug exposure, although the decrease was less prevalent with additional dosing. 

The authors hypothesized the possible rationale underlying these effects: “The acid labile nature of esomeprazole may explain the decreased bioavailability. Under fed conditions, food delays gastric emptying...and esomeprazole degradation increases with increased time in the stomach,” they wrote.

Bottom line: If you want your PPIs to work against heartburn, it’s probably a good idea to refrain from eating a high-calorie breakfast of bacon and eggs before taking them.

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