# Are polypharmacy side effects predicted by public data still valid in real-world data?

## TL;DR

This study confirms that predicted drug interactions from public data match real-world patient outcomes, showing that combining cefpodoxime and chlorpheniramine increases lung edema risk.

## Contribution

The study validates predicted polypharmacy side effects using real-world patient data, showing their clinical relevance.

## Key findings

- Patients taking cefpodoxime and chlorpheniramine together had a higher risk of lung edema than those taking either drug alone.
- Real-world data confirmed the prediction model's findings about the cefpodoxime-chlorpheniramine-lung edema interaction.
- Using real-world data improves the accuracy of adverse event prediction models for drug combinations.

## Abstract

Although interest in predicting drug-drug interactions is growing, many predictions are not verified by real-world data. This study aimed to confirm whether predicted polypharmacy side effects using public data also occur in data from actual patients.

We utilized a deep learning-based polypharmacy side effects prediction model to identify cefpodoxime-chlorpheniramine-lung edema combination with a high prediction score and a significant patient population. The retrospective study analyzed patients over 18 years old who were admitted to the Asan medical center between January 2000 and December 2020 and took cefpodoxime or chlorpheniramine orally. The three groups, cefpodoxime-treated, chlorpheniramine-treated, and cefpodoxime & chlorpheniramine-treated were compared using inverse probability of treatment weighting (IPTW) to balance them. Differences between the three groups were analyzed using the Kaplan-Meier method and Cox proportional hazards model.

The study population comprised 54,043 patients with a history of taking cefpodoxime, 203,897 patients with a history of taking chlorpheniramine, and 1,628 patients with a history of taking cefpodoxime and chlorpheniramine simultaneously. After adjustment, the 1-year cumulative incidence of lung edema in the patient group that took cefpodoxime and chlorpheniramine simultaneously was significantly higher than in the patient groups that took cefpodoxime or chlorpheniramine only (p=0.001). Patients taking cefpodoxime and chlorpheniramine together had an increased risk of lung edema compared to those taking cefpodoxime alone [hazard ratio (HR) 2.10, 95% CI 1.26–3.52, p<0.005] and those taking chlorpheniramine alone, which also increased the risk of lung edema (HR 1.64, 95% CI 0.99-2.69, p=0.05).

Validation of polypharmacy side effect predictions with real-world data can aid patient and clinician decision-making before conducting randomized controlled trials. Simultaneous use of cefpodoxime and chlorpheniramine was associated with a higher long-term risk of lung edema compared to the use of cefpodoxime or chlorpheniramine alone.

•Validating polypharmacy side effect predictions with real-world data informs patient and clinician decision-making.•Concurrent use of cefpodoxime and chlorpheniramine raises lung edema risk compared to each drug alone.•Utilizing real-world data is essential for improving adverse event prediction models' capability.

Validating polypharmacy side effect predictions with real-world data informs patient and clinician decision-making.

Concurrent use of cefpodoxime and chlorpheniramine raises lung edema risk compared to each drug alone.

Utilizing real-world data is essential for improving adverse event prediction models' capability.