Purpose: Posaconazole (POS) is an oral triazole agent that has broad-spectrum activity against filamentous fungi. POS demonstrates a concentration to response relationship for the treatment of invasive fungal infections (IFI), but many factors limit its absorption and serum concentrations. Methods: We retrospectively reviewed all heart and lung transplant recipients at our center from Jan 2008 to Sept 2009 who had at least one serum POS level measured. Results: 22 serum POS levels were available for evaluation. 73% were for treatment of proven/probable IFI and 27% for prophylaxis post-transplant. The median time from the initiation of POS to drug level was 14.5 days. 41% of the levels were associated with 200 mg QID administration, 23% with 200 mg TID, 18% with 300 mg QID, 14% with 400 mg BID, and 5% with 400 mg QID. All patients received acid suppressive therapy and 45% had normal appetite. 36% of patients were fed via gastric tubes. The mean and median plasma concentrations were 0.51 and 0.67 g/ml, respectively (range: 0.13-2.54). 45% of the levels were 1 g/mL. Patients with levels > 1 g/mL were older (median age 68 vs 56; p=0.04), more nutritionally independent (78% vs 23%; p=0.03), and more likely to receive TID rather than QID administration (40% vs 0%; p=0.05). Among 6 patients treated with POS for IFI, only 2 achieved levels >1ug/ml. In 2 patients POS was stopped due to persistently low levels. No patient with a proven/probable IFI treated with POS had a complete response at 6 weeks. Diarrhea was the most common adverse event, occurring in 4/10 patients. Conclusions: POS use in heart/lung transplant recipients continues to be a challenge given the severity of underlying illness and variable dietary compliance. Appropriate serum concentrations have been associated with improved outcomes, but may not be obtainable in all patients. Clinicians are urged to correct modifiable patient factors that may affect oral absorption and to rely on therapeutic drug monitoring to guide therapy with POS.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)