Role of Therapeutic Drug Monitoring: EVALUATION OF RESPONSE

pharmacokinetics

The next question to be considered is whether the drug’s pharmacologic response is not readily assessable, in terms of both efficacy and toxic effects.

Efficacy

With the increasing prevalence of invasive fungal infec­tions and the emergence of rare pathogens, the diagnosis of fungal infections remains challenging and controversial. Comorbidities such as immunosuppression and neutropenia in patients who are prone to this type of infection may complicate the diagnosis by masking key signs and symptoms. canadian cialis online

A definitive diagnosis of invasive fungal infection usually requires positive findings on histopathologic or cytopathologic examination, with demonstrated growth of the offending pathogens. However, the results of such examinations can be falsely negative in patients who are already receiving antifungal therapy. Furthermore, certain patients may not be candidates for invasive diagnostic procedures because of concerns about hemodynamic instability. Thus, in most circumstances, the diagnosis of invasive fungal infections is based largely on the likelihood of such an infection. Even then, there is no consensus on how the probability of infection should be derived and how this should guide therapy. The Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer has released an international consensus statement on defining opportunistic invasive fungal infections; however, the guideline is intended for research purposes and for use with immuno- compromised patients with cancer and hematopoietic stem cell transplantation.

The recommended approach to monitoring therapeutic response in patients with invasive fungal infections is to regularly assess the clinical, mycological, radiographic, or histopathologic signs and symptoms that were positive at the time of diagnosis. This may involve serial computed tomography of the chest for patients with invasive pulmonary aspergillosis or repeat biopsy of the infection site. A composite of parameters should be adopted, instead of a single monitor­ing end point, because in some cases it may become difficult to differentiate infection from colonization.
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Toxic Effects

Voriconazole is generally well tolerated, with the most frequently reported adverse events being visual disturbances, fever, rash, vomiting, nausea, headache, and diarrhea. The most common treatment-related adverse effects leading to discontinuation of therapy are elevated liver function, rash, and visual disturbances.

In a postmarking analysis based on the French pharma- covigilance database, the most frequently reported adverse drug events among patients receiving voriconazole were liver function abnormalities (23%), visual disturbances (18%), skin rashes (17%), neurologic disturbances (14%), cardiovascular events (10%), hematologic disorders (8%), and renal disturbances (4%). According to the Naranjo criteria, 84% of these events were classified as possible drug-related effects, 7% as probable, 5% as highly probable, and 4% as doubtful. cialis soft tabs

Category: Drugs

Tags: antifungal, invasive fungal infection, pharmacokinetics, therapeutic drug monitoring, voriconazole

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