DDI of the Month Podcast

In this 10th edition of DDI of the Month, host Prof. dr. David Burger welcomes dr. Joe Piscitelli from Pfizer, USA, for an in-depth discussion on the DDI profile of encorafenib.

Encorafenib is a potent and selective small-molecule inhibitor of BRAF V600-mutant kinase, and approved for various malignancies, including non-small cell lung cancer. 

Based on in vitro research there was uncertainty about the DDI potential of encorafenib as a precipitant drug. Piscitelli et al. conducted a so-called cocktail study to answer this question. 

The study results have recently been published in Clinical Pharmacology & Therapeutics journal: An Evaluation of the Drug Interaction Potential of Encorafenib in Combination With Binimetinib Using the Inje Cocktail in Patients With Cancer.

Tune in to hear about:

• What is the Inje cocktail and how does it differ from other cocktails?
• What is the effect of encorafenib on various CYP450 enzymes tested in this cocktail study?
• What were the challenges with using caffeine as a CYP1A2 probe?
• Does binimetinib play a role in the DDI profile of its combination with encorafenib?
• Which effects of encorafenib can be expected on drug transporters as they are not included in the Inje cocktail?
• Can encorafenib also be the object of a DDI, or is it only a precipitator?

An insightful episode for clinicians, pharmacists, and researchers involved in managing and studying drug–drug interactions. Don’t miss it—listen now!

In this ninth edition of DDI of the Month, host Prof. dr. David Burger welcomes two leading experts from Switzerland, Dr Claire Coumau and Dr Chantal Csajka, for an in-depth discussion on P-glycoprotein (P-gp)–mediated drug–drug interactions.

The episode is centered around their recent publication in Clinical Pharmacokinetics: “A Systematic Review and Classification of the Effects of P-glycoprotein Inhibitors and Inducers in Humans, Using Digoxin, Fexofenadine, and Dabigatran as Probe Drugs.”

P-glycoprotein plays a key role in drug absorption and disposition, yet its interaction potential has long been less clearly defined than that of hepatic enzymes such as CYP3A. In this conversation, the authors explain why they set out to systematically review human data, propose a clinically meaningful classification of P-gp inhibitors and inducers, and highlight important similarities — and differences — between P-gp and CYP3A interactions.

Tune in to hear about:

• Why a human-only systematic review of P-gp interactions was needed
• How P-gp inhibitors and inducers can be classified using exposure-based criteria
• Which drugs qualify as moderate or potent P-gp inhibitors or inducers
• Why strong P-gp modulators are relatively rare compared to CYP3A modulators
• The concept of short-term inhibition followed by time-dependent induction
• The role of probe drugs such as digoxin, dabigatran, fexofenadine—and the potential of edoxaban

An insightful episode for clinicians, pharmacists, and researchers involved in managing and studying drug–drug interactions. Don’t miss it—listen now!

 
DDI of the Month returns with Episode 8! Tune in as we explore new data on the metamizole-quetiapine interaction and its clinical impact.
In this episode of DDI of the Month, we’re excited to welcome two distinguished quests from Germany: Dr. Arnim Gaebler and Dr. Michael Paulzen. Together, we dive into their recent published paper in the British Journal of Clinical Pharmacology, titled: “Discovering interactions in polypharmacy: Impact of metamizole on the metabolism of quetiapine”

Metamizole, a widely used analgesic in several European countries, has long been considered safe in acute care. However, with an increasing number of indications for chronic use being explored, managing potential drug interactions is becoming more important. Despite being on the market for decades, little is known about metamizole’s interaction potential.

New evidence suggests that metamizole may substantially reduce plasma concentrations of quetiapine – an antipsychotic frequently prescribed in psychiatric and geriatric populations – by more than 50%. The likely mechanism? Induction of CYP3A4, the key enzyme responsible for quetiapine metabolism.

Tune in to hear:
•The motivation behind the study
•Surprising finding from the KONBEST database analysis
•Why metamizole may be a stronger enzyme inducer than previously though
•The implications for therapeutic drug monitoring (TDM)
•How these finding could influence prescribing practices in psychiatry

Don’t miss this insightful conversation – listen now!

In the seventh episode, Prof. Dr. David Burger discusses with Nicki Kyriacou the review article: “Green tea catechins as perpetrators of drug pharmacokinetic interactions”. 

You might think: “Green tea?– I drink it all the time! “But is it really that innocent?
Tune in now as we explore how catechins-compounds found in green tea, like (-)-epigallocatechin-3-gallate – can impact drug pharmacokinetics. These compounds can alter drug solubility, transporter activity, and metabolism, potentially affecting the concentration of therapeutic drugs such as atorvastatin, digoxin, and sildenafil.

The following key topics will be discussed in the podcast:

• The scope and intensity of green tea interaction studies;
• Different green tea formulations and their impact on drug interactions;
• Relevance for specific patient populations (especially cardiovascular medications);
• Why green tea reduces most drug concentrations – but increases sildenafil levels;
• The role of timing in green tea consumption vs. co-medication; and
• Practical guidance for clinicians and pharmacists to assess potential interaction.

Don’t miss this insightful discussion on the drug interaction potential of green tea and the practical takeaways for health professionals!

In this episode of the DDI of the Month podcast, Dr. David Burger dives into a critical topic: P-glycoprotein (P-gp)-mediated Drug-Drug Interactions with Dr. Leonie Bogaard. Join us as we explore the role of P-gp, a key transporter involved in drug absorption and elimination, and its impact on clinical outcomes.

In this episode, we discuss:
•    How P-gp modulation affects systemic drug exposure.
•    The challenges in managing DDIs due to overlap with enzymes like CYP3A4.
•    Practical recommendations for identifying and addressing P-gp-related DDIs in clinical settings.

Don’t miss this engaging discussion, featuring insights from recent research and expert recommendations on improving patient care while minimizing risks.​​​​

In our latest episode, we dive into an important study by Dr. Massimo and Dr. Gianluca which examins the agreement between different drug interaction checkers (ICs) when evaluating interactions involving widely used proton pump inhibitors (PPIs). 

PPIs are frequently prescribed for treating acid-related conditions and preventing medication-induced ulcers, especially in older patients with multimorbidity and polypharmacy. These interactions are often complex, involving increased gastric pH (reduction of absorption) and metabolism through CYP3A4 and CYP2C19 enzymes. However, this study reveals significant inconsistencies between the summary of product characteristics (SPCs) and five individual widely-used ICs.   

The podcast covers:  
- How different ICs (like INTERCheck WEB, Micromedex, Lexicomp, Epocrates, and drugs.com) identify and classify potential interactions with PPIs (including omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole).
- The alarming discrepancies between the IC data and official product summaries (SPCs), and how this impacts clinical decision-making. 
- Why healthcare professionals should use multiple sources and collaborate closely in managing complex medication regimens, especially in elderly patients. 

Listen to learn more about the findings of this study and how to improve patient safety and ensure the accurate identification of drug interactions that can affect patient outcomes.

The fourth episode will delve into the use of artificial intelligence (AI) to optimize medication alerts generated by clinical decision support systems (CDSSs). David Burger will discuss the review findings and future opportunities with Jetske Graafsma and Dr. Patricia van den Bemt.
 
Medication safety is crucial, and preventing adverse drug events (ADEs) is a key aspect. Clinical decision support systems (CDSSs) in electronic health records help reduce the risk of ADEs by generating alerts for dosages, DDIs, contraindications, duplicate therapies, drug allergies, and intolerances. However, the high volume of alerts can lead to alert fatigue, potentially causing important alerts to be missed. 

In a recent scoping review, Graafsma et al. provided an overview of 10 studies on the application of AI to optimize medication alerts from CDSSs in hospital settings. AI is a promising yet relatively new healthcare tool, and thorough external validation is often needed before its implementation.

The upcoming podcast will discuss the review findings, AI’s potential for improving CDSS, and its practical implementation. We’ll also hear Jetske and Patricia’s insights on alert fatigue and future research opportunities.

In the third podcast, Dr. Burger discusses the added value of reporting outcomes of real-world cases in patients with HIV caused by drug-drug interactions (DDIs) with Dr. Ambrosioni and Dr. Molto.

Several databases are available for DDI management, with discrepancies often occurring between the databases. The differences may be caused by extrapolations from studied interactions to predict the DDI potential for unknown drug combinations. The relevance of the unstudied DDIs is often unknown.

Reporting the outcomes of real-world cases can determine the relevance of DDIs. The article discusses real-world cases between antiretrovirals (ARVs) and comedications reported on www.clinicalcasesDDIs.com. Twenty percent of the reported cases involve over-the-counter drugs, which are often not recorded in patient files.

The following topics will be discussed during the podcast:
- the challenges of DDI management of ARVs with comedications;
- the added value of reporting outcomes of real-world cases; and
- the underestimated risks of over-the-counter (OTC) drug use.

Listen to the podcast for all the tips and take-home messages!

Read the full article here: https://link.springer.com/article/10.1007/s40121-024-00935-0

In the second episode of this podcast series, Dr. Malone, Dr. Gómez-Lumbreras, and Dr. Burger will discuss the drug-drug interaction potential of colchicine, which may be underestimated. 

Dr. Malone’s research group did a study on real-world data on the interaction potential of colchicine. Colchicine concentration can be increased by CYP3A4 inhibitors, which may lead to toxicity and adverse events. Adverse events cases reported between 2004 and 2020 were studied for the involvement of colchicine in DDIs. In 66% of 787 studied reports, colchicine was identified as a concomitant drug.  This indicates that the reporter did not think colchicine was the cause of the adverse events mentioned in the reports. 

• Could colchicine possibly play a bigger role in DDIs than currently thought? 
• Are there any safety concerns of colchicine use combined with strong CYP3A4 inhibitors? 
• And what practical guidance is needed for the safe use of colchicine in combination with other medicines?

Listen to the second episode of DDI of the Month to find out!

In the first exciting episode of this new podcast series, Dr. Iversen and Dr. Burger will dive into DDIs with flucloxacillin, and explore the results of Dr. Iversen's research trial.

Dr. Iversen’s research group has studied the extent of induction of flucloxacillin of the CYP enzymes in healthy adults and 3D spheroid of primary human hepatocytes (PHHs). The research group performed a randomized, unblinded, two-period, cross-over, clinical pharmacokinetic (Basel) cocktail study with twelve healthy adults. During the podcast, the study will be discussed in detail.

Find out the interesting results of this study!