Ceftriaxone/Lansoprazole Combo Linked to Potentially Fatal Heart Condition

‘Big data’ reveal risky drug pairs

Researchers at Columbia University Medical Center and the Data Science Institute at Columbia University have uncovered a potentially dangerous drug interaction using data science. Their findings were published in the Journal of the American College of Cardiology (JACC).

Safe when taken on their own, some prescription drugs become deadly when combined. Many of these interactions are well known, but others remain hidden to doctors, drug companies, and patients. Identifying these risky combinations has become a priority as the number of Americans on multiple medications rises.

Leveraging the power of big data, the researchers found a way to expand and improve the search for drug interactions. Mining a government database of reported drug adverse effects and a university hospital archive of patient records, they discovered eight pairs of drugs that were associated with a higher risk of a potentially deadly heart condition. Testing one of the pairs on individual heart cells in the lab, they discovered why the drug combination may disrupt the heart’s normal electrical activity in some patients.

The pair of drugs that the researchers studied—the antibiotic ceftriaxone (Rocephin, Roche) and the heartburn medication lansoprazole (Prevacid, Takeda)—are widely prescribed, and alone carry no known heart-related risks. But together, they may increase the chance that patients develop a heart condition known as long QT syndrome, which can cause abnormal heart rhythms and, in rare cases, sudden death, according to the investigators. The study found that patients taking ceftriaxone and lansoprazole together were 1.4 times more likely to have a prolonged QT interval than were patients who were taking either drug alone.

“What’s most surprising is that you can go from a database of billions of data points to making a prediction that two molecules together can change the functions of a protein in a single heart cell,” said senior author Nicholas Tatonetti, PhD.

Looking at adverse effects alone, the algorithm identified hundreds of suspect drug pairs. To narrow the search, the researchers turned to a Columbia database of patient records to see if the drug pairs produced measurable effects on the heart. Consulting the electrocardiograms of patients in the database, they found the QT prolongation signal with several dozen drug pairs.

Of the four pairs with the largest effect, the researchers tested the most widely used combination first: ceftriaxone and lansoprazole.

As anticipated, neither drug on its own had an effect on the electrical pathway known as the hERG channel, which helps the heart maintain a normal rhythm. When combined, however, the drugs blocked the channel’s electrical signal, which is responsible for maintaining a normal QT interval.

The researchers have informed the FDA and the companies that discovered the drugs––Roche for ceftriaxone and Takeda for lansoprazole––of their findings and are preparing to test the other three pairs of drugs.

In an editorial published in the same issue of JACC, Dan Roden, MD, of Vanderbilt University Medical Center cautioned that the findings were not yet conclusive enough for doctors to advise all patients, or even patients at risk for QT prolongation, to avoid the drug pair. But he expressed support for the approach, and recommended that the authors consider conducting a small clinical trial to confirm the interaction.

Source: Columbia University Medical Center; October 10, 2016.