Managing drug interactions in the patient with aspergillosis

Drug interactions are a common and recurring problem in immunocompromised patients with aspergillosis. While the introduction of new antifungals has expanded opportunities for lowering drug toxicity, virtually all antifungal regimens still carry the risk for pharmacokinetic and pharmacodynamic interactions. Drug interactions affecting the pharmacokinetics of antifungals used in the treatment of aspergillosis, or interactions that decrease the metabolism/elimination of a drug with a narrow index for efficacy (e.g. anti-retroviral therapy) or safety (e.g. immunosuppressants, chemotherapy) have the greatest potential to cause serious harm. Additionally, azole-based treatment regimens for aspergillosis carry a risk for uncommon, but potentially life-threatening, interactions that affect cardiac conduction leading to severe tachyarrythmias such as Torsades des Pointes. Clinical diagnosis of antifungal drug interactions in immunocompromised patients remains a challenge, as adverse sequelae are often masked by infection or other drug therapies (especially chemotherapy). Therefore, a high index of suspicion and a proactive, multidisciplinary approach is essential for preventing drug interactions in patients with aspergillosis. Improvements in laboratory support (i.e. patient pharmacogenetic profiling, expanded use of serum drug level monitoring) will become increasingly important for managing drug interactions patients on complex treatment regimens.