The ECCMID 2024 congress was held in Barcelona from April 27 to 30. The weather in Barcelona was disappointing, but that was all the more reason to attend the sessions and absorb the wealth of information. There were many interesting sessions, and below, I have summarized the results of some drug interaction studies presented at ECCMID 2024.

• Pharmacokinetics of zoliflodacin in healthy participants in the presence of itraconazole suggest no clinically meaningful CYP3A4-mediated drug-drug interactions(A. Luckey et al.):

Zoliflodacin (substrate of CYP3A4) is an experimental drug for the indication of uncomplicated gonorrhea. An open-label, 2-period, 2-treatment, fixed sequence crossover DDI study was performed to assess the effect of a potent CYP3A4 inhibitor, itraconazole, on the pharmacokinetics of zoliflodacin (dose: 3 grams). Itraconazole increased zoliflodacin exposure by 1.03-, 1.39-, and 1.38-fold for Cmax, AUC(0-last), and AUC(0-inf), respectively. This increase is unlikely clinically significant due to previously observed exposures in the clinical development program and the overall safety profile of zoliflodacin at higher doses.

• Impact of multiple-dose remdesivir, a COVID-19 antiviral, on CYP3A4 activity: a clinical drug-drug interaction (DDI) study with midazolam (A. Shaik et al.):

Remdesivir is an approved treatment for COVID-19 in adults. In-vitro studies show that remdesivir is a weak inhibitor of CYP3A4. This study evaluated the induction potential on CYP3A4 of a 10-day regimen of remdesivir on probe midazolam (CYP3A4 substrate). They found an increase of 1.30-, 1.31-, and 1.45-fold in the AUCinf, AUClast, and Cmax of midazolam, respectively. This increase is unlikely clinically relevant, and remdesivir is safe to use.

• Drug interactions with nirmatrelvir/ritonavir in hospitalized patients: prevalence, severity and management strategies (S. Swaid et al.): Nirmatrelvir/ritonavir can be used for the treatment of mild-to-moderate COVID-19 infection in patients with a high risk of progression to severe disease. Ritonavir is a potent CYP3A4 inhibitor and has the potential for many drug-drug interactions (DDIs). This study describes the policy, prevalence, severity, and management strategies of DDIs with nirmatrelvir/ritonavir. 192 of 247 (78%) observed patients had a potential for at least one clinically relevant DDI for which an action is required. 361 interacting drugs were identified. To combine nirmatrelvir/ritonavir with comedications, screening for clinically relevant DDIs and managing the DDIs is essential before starting treatment.

• The influence of concurrent low-dose oral calcium carbonate supplementation on steady-state pharmacokinetics of once-daily oral raltegravir (L. Porto):

Raltegravir is commonly used in combination with anti-retroviral therapy for HIV treatment. Calcium supplement is recommended to mitigate bone mineral density loss and an over-the-counter drug, which means this supplement is only sometimes reported in patient files. In previous studies, it was found that calcium supplements significantly decrease raltegravir exposure. This study characterizes raltegravir pharmacokinetics in steady-state in patients with HIV and determines if the target concentrations of raltegravir are achieved. The C24 of raltegravir decreased more than 30% by coadministration of calcium supplements, but this was unlikely clinically relevant. The mean levels of raltegravir were within the expected or target therapeutic values range.

On April 28, Laura Nijboer presented a poster (see below) on the topic: drug-drug interaction potential of the novel CMV drugs Letermovir and Maribavir. Letermovir and maribavir are novel anti-cytomegalovirus agents, also known as CMV agents. These CMV drugs have mainly been beneficial to transplant recipients receiving immunosuppressive therapy. These patients often have polypharmacy and, therefore, an increased risk for DDIs. It is thus crucial for clinicians to have insight into the DDI management of these novel CMV agents. This study found that 17.4% of the comedications have a clinically relevant interaction with letermovir. 5.6% of the comedications are contraindicated for combined use with letermovir. For maribavir, the numbers are 10.6% and 1.2%. Both letermovir and maribavir can be involved in many DDIs, and therefore, DDI management is necessary. We included all DDIs with recommendations in an online tool to guide clinicians. You can look at all DDIs of letermovir and maribavir on the CMV DDI Manager.