Systemic Drug–Drug Interactions in Dental Care: Patterns, Risks, and Clinical Management Strategies ^†

In the context of an aging population and the increasing number of patients receiving multiple medications, modern dental practice faces the growing challenge of drug–drug interactions (DDIs). These interactions can have serious clinical consequences, particularly in patients with cardiovascular comorbidities. Theoretical DDI-related risks are well understood; however, there is limited real-world data on the frequency and severity of drug–drug interactions (DDIs) in dental care, which impedes the implementation of adequate preventive strategies.

Our recent retrospective study aimed to address this gap by evaluating the prevalence and severity of DDIs in a cohort of 105 patients treated at a dental clinic [1]. The researchers also aimed to identify risk patterns related to age and cardiovascular disease (CVD), proposing clinical strategies to reduce harm from drug–drug interactions (DDIs). The study included only patient data containing at least two drugs. We checked all possible drug pairs with DrugBank [2].

The results revealed that 40.7% of tested drug pairs resulted in interactions, including 2.3% classified as major, 25% classified as moderate, and 13.4% classified as minor interactions. Notably, no major DDIs were observed in patients under 30 years of age. However, the 31–60 age group accounted for 61.3% of all major DDIs, while the 61 and above age group accounted for 38.7% of DDIs. Patients with CVD had a significantly higher DDIs burden, with a median of 18 interactions compared to 10 in those without cardiovascular conditions [1].

Epinephrine is one of the most widely used vasoconstrictor drugs in dental anesthetics; DDIs involving epinephrine and beta-blockers (e.g., metoprolol and nebivolol) raise significant concerns. These combinations may increase the risk of hypertensive episodes or other dangerous cardiovascular events [3]. These specific clinical contexts require low doses of epinephrine or alternative anesthetics, such as mepivacaine or phenylephrine. Also, the inhibitory effects of epinephrine on CYP3A4 may increase the toxicity of cardiovascular disease drugs such as amiodarone, highlighting the need to avoid this vasoconstrictor when possible. Other high-risk combinations revealed by our dataset include ibuprofen with spironolactone or methotrexate, which increase the risk of hyperkalemia; in these cases, acetaminophen or tramadol are safer alternatives for ibuprofen. Also, the use of spironolactone with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) requires reduced doses of ibuprofen, minimal doses of nonsteroidal anti-inflammatory drugs (NSAIDs), and monitoring of renal function. [3,4,5].

To improve safety, our study proposed a routine use of medication reconciliation, DDI-checking tools, and interdisciplinary collaboration. We developed a decision support algorithm to guide the appropriate use of epinephrine-containing anesthetics in patients with complex medication profiles [1].

Our data-driven real-world study reveals a significant burden of DDIs in older and CVD dental patients. DDIs screening, adjusted therapy plans, and collaboration between dentists and pharmacists are essential for safer and more personalized dental care [1,6].