(692) PDE5 Inhibitors and Drug Interactions, Medical Review

Introduction Drug interactions with PDE5 inhibitors can occur through pharmacokinetic or pharmacodynamic pathways. The most common pharmacodynamic interactions (which potentiate the effect of another medication) are with organic nitrates and alpha-adrenergic blockers. The main pharmacokinetic interactions generally involve the cytochrome P450 metabolic pathway, particularly the CYP3A4 isoenzyme. Objective The objective of this systematic review was to study drug interactions with phosphodiesterase type 5 (PDE5) inhibitors to minimize adverse events, especially cardiovascular events, and assess patient safety in clinical practice. Methods A systematic search was performed in PubMed/MEDLINE, SciELO, LILACS, Embase, and the Cochrane Library from inception to January 2000. Information on major side effects, dosing and drug interactions was obtained. Results Eleven articles were reviewed. Potentially dangerous pharmacodynamic interactions with nitrates and alpha-blockers were identified. Pharmacokinetic interactions (CYP3A4 isoenzyme) were also prevalent; potent inhibitors (e.g., Ritonavir, macrolide antibiotics, and azole antifungals) increase plasma concentrations, raising the risk of adverse effects. Conclusions Although PDE5 inhibitors are considered safe for most patients, interactions with nitrates pose a substantial risk. A detailed patient history is essential to identify concomitant use of antihypertensives, nitrates, alpha-blockers, and CYP3A4 enzyme inhibitors or inducers. Patient education about the risks is crucial to treatment safety. Disclosure No