Cookie policy: This site uses cookies (small files stored on your computer) to simplify and improve your experience of this website. Cookies are small text files stored on the device you are using to access this website. For more information please take a look at our terms and conditions. Some parts of the site may not work properly if you choose not to accept cookies.

Join

Subscribe or Register

Existing user? Login

Drug–drug interactions

Study highlights drug-drug interaction risk from two commonly used drugs

Patients who take the antibiotic ceftriaxone and the proton pump inhibitor lansoprazole at the same time are at increased risk of drug-induced arrhythmia, study finds.

Electrocardiogram trace

Source: Shutterstock

An increased risk of drug-induced arrhythmia (electrocardiogram trace pictured) can result from an interaction between the antibiotic ceftriaxone and the proton pump inhibitor lansoprazole

Combined treatment with the antibiotic ceftriaxone and the proton pump inhibitor (PPI) lansoprazole can lead to an increased risk of drug-induced arrhythmia, a study has found.

The research, which used a combination of adverse event data-mining, electronic health record analysis and laboratory experiments, found that patients who received both drugs together were more likely to experience drug-induced long QT syndrome (LQTS), a potentially fatal condition, than those who received either drug alone.

The research team first used algorithms to trawl a database of 1.8 million adverse event reports collected by the US Food and Drug Administration to look for evidence of unexpected drug–drug interactions.

“These algorithms are similar to what technology companies like Google and Facebook use to target [advertisements] to users, except in our case we are attributing adverse reactions to drug combinations,” explains lead author Nick Tatonetti, an assistant professor of biomedical informatics at Columbia University in New York.

After accounting for confounding, the analysis identified a list of eight drug combinations not previously linked to acquired LQTS that produced safety signals, one of which was the ceftriaxone/lansoprazole combination.

The team then attempted to verify this signal using electronic health records for 382,221 patients who had undergone 1.6 million electrocardiograms between 1996 and 2014. Using these data, the researchers created three cohorts according to patients’ exposure to the drugs: those who had received both drugs within a seven-day period; those who only ever received ceftriaxone; and those who only ever received lansoprazole. They then compared corrected QT intervals for these patients that had been measured within 36 days of drug exposure.

The researchers found that the drug combination resulted in longer QT intervals in both sexes: by an average of 12ms in men and by 9ms in women. Additional stratification for race showed that the effect was greatest in white men and black women, with an average prolongation of 12ms for both groups.

A greater proportion of patients who received the ceftriaxone/lansoprazole combination had a QT interval of at least 500ms, a clinically relevant threshold. For example, 19.3% of men who received the combination surpassed this threshold compared with 14.2% of those receiving ceftriaxone only and 12.8% receiving lansoprazole only.

The researchers found further support for their findings in laboratory experiments. They used patch-clamp electrophysiology to examine the effects of the drugs on cells expressing the hERG channel. This channel is involved in the heart’s electrical activity and is frequently blocked by drugs that cause LQTS.

The team showed that, although ceftriaxone had no effect on the channel, when added in the presence of lansoprazole it resulted in a dose-dependent drop in current.

“Our data support the hypothesis that ceftriaxone and lansoprazole increase the risk of acquired LQTS in patients and that they do so through the hERG channel, an important ion channel in the heart,” says Tatonetti.

The researchers, who report their findings in the Journal of the American College of Cardiology[1] (online, 10 October 2016), note that both drugs would comfortably satisfy regulatory safety requirements for drug approval individually but, given the extent to which they were able to block the hERG channel, would be unlikely to receive approval if submitted to regulators as a combination.

Sean Hennessy, a professor of epidemiology at the University of Pennsylvania in Philadelphia, says that identifying drug-drug interactions is challenging because clinical trials often include patients who are younger and taking fewer medications than those who go on to receive the treatment in clinical practice.

Hennessy says the researchers’ approach – combining three independent types of data – shows promise as a way to prioritise drug combinations for potential interactions. The interaction between ceftriaxone and lansoprazole needs further examination, he adds. “I believe that the study raises a hypothesis that deserves to be confirmed or refuted, but don’t believe the evidence is strong enough at this point to be clinically actionable.”

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2016.20201821

Readers' comments (1)

  • This is v important, and raises the question as to whether other proton pump inhibitors have the same adverse effect when in combination with ceftriaxone. We should keep in mind that proton pump inhibitors are frequently used haphazardly without a real medical indication.
    Also, assessing that is crucial in the pediatric age group while proton pump inhibitors are used in plethora( often also unnecessarily) for a presumptive GE reflux, and frequently there is concomitant use of ceftriaxone for otitis media for instance-even outside hospital settings.

    Unsuitable or offensive? Report this comment

Have your say

For commenting, please login or register as a user and agree to our Community Guidelines. You will be re-directed back to this page where you will have the ability to comment.

Recommended from Pharmaceutical Press

  • Drugs in Use

    Drugs in Use

    Optimise drug therapy for your patients. These case studies help you bridge the gap between theoretical medicines knowledge and practical applications.

    £42.00Buy now
  • Stockley's Drug Interactions

    Stockley's Drug Interactions

    Now in its eleventh edition, Stockley’s Drug Interactions is still the most comprehensive and authoritative international source of drug interaction information.

    £205.00Buy now
  • Stockley's Drug Interactions Pocket Companion

    Stockley's Drug Interactions Pocket Companion

    The 2016 pocket guide to drug interactions and their management, for the busy healthcare professional.

    £29.95Buy now
  • Disease Management

    Disease Management

    Disease Management covers the diseases commonly encountered in primary care by system, with common therapeutic issues. Includes case studies and self-assessment sections.

    £52.00Buy now
  • Workplace Drug Testing

    Workplace Drug Testing

    Explains drug testing regulatory frameworks and all aspects of drug analysis. Case studies of successful programmes are included.

    £79.00Buy now
  • Aromatherapy Science

    Aromatherapy Science

    Science-based aromatherapy information for healthcare professionals. Includes monographs on the commonly used essential oils.

    £42.00Buy now

Search an extensive range of the world’s most trusted resources

Powered by MedicinesComplete
  • Print
  • Share
  • Comment
  • Save
  • Print Friendly Version of this pagePrint Get a PDF version of this webpagePDF

Supplementary images

  • Electrocardiogram trace

Newsletter Sign-up

Want to keep up with the latest news, comment and CPD articles in pharmacy and science? Subscribe to our free alerts.