Drug-Drug Interactions in Oncology

Chemotherapy drugs can interact with one another or – more precisely – have effects on body tissue that are complementary or work sideways to the effects of other drugs.  Drug-drug interactions (DDIs) are common and of concern to medical professionals.

DDIs show up more often in the elderly if only because the elderly tend to take more medicines.

Not all drug interactions are detrimental or wholly detrimental.  Sometimes the interaction increases the efficacy or one or more drugs, and sometimes there is a positive outcome that would not be expected from just one of the drugs.  Indeed, combination chemotherapy could be considered a form of intentional DDI.

Drug interactions are of concern in all areas of medicine – observers estimate 20 to 30 percent of adverse reactions are due to interactions among drugs. They are of particular concern in oncology because the therapeutic index of the drugs tends to be low.

Doctors also have to keep these interactions in consideration when they set the dose for a patient.  It’s a major part of the reason determining an optimal dose is so difficult. Aside from the medicines the doctor or team of doctors prescribes, other supplements taken by a patient (over-the-counter or herbs) may produce interactions.

Food interactions are also possible and of increased concern as oral oncology drug are being used more often.  Like other chemotherapy medicines, the oral ones have narrow therapeutic windows and food can possibly affect their metabolism.  The bioavailability of kinase inhibitors is known to be affected by whether the patient also takes statins (cholesterol medications), antacids, proton pump inhibitors (for acid reflux), and other medicines.

Nurse administering chemotherapyPharmacokinetic (how fast the drugs get to the tissue undergoing the reaction and how fast the body eliminates both drugs) mechanisms are the hallmarks of some DDIs.  If the two drugs work the same way at the biochemical level, the interaction could produce a boosted efficacy or a possibly dangerous increase in toxicity.  This is a pharmacodynamic DDI.

Individual patient physiologies come into play and whether a DDI shows up in any patient (and if so, how big it is) can vary.

Some things about DDIs

The clinical trials pharmaceutical companies conduct before releasing new medicines to the market often fail to find DDIs because they are not looking for them, and because they are designed to be clean – patients taking other medicines are often excluded from the trials.  It’s not until the medicine is being used by real life patients in real life situations that they come to light.

It is difficult to identify a true DDI.  The observed phenomenon might be a side effect of one of the drugs rather than the result of two medicines.  Or the natural symptom of the cancer (or another disease) might be the reason. And collecting evidence from patients in the field is difficult because it is anecdotal evidence and the geographic dispersion of the patients makes it hard to compare symptoms.