Amantadine/Oseltamivir/Ribavirin

Antiviral resistance among influenza A viruses is associated with high morbidity and mortality in immunocompromised hosts. However, treatment strategies for drug-resistant influenza A are not established. A triple-combination antiviral drug (TCAD) regimen consisting of amantadine (AMT), oseltamivir (OSL) and ribavirin (RBV) demonstrated good efficacy in an animal model.

We first analysed the pharmacokinetics (PKs) of TCAD therapy in healthy volunteers. We then performed a pilot study of TCAD therapy in patients undergoing chemotherapy or haematopoietic cell transplantation. AMT (75 mg), OSL (50 mg) and RBV (200 mg) were administered three times a day for 10 days. The safety and PKs of TCAD therapy were monitored.

The PKs of TCAD therapy in healthy volunteers was shown to be similar to the PKs of each drug individually from a single dose. In the pilot study, six immunocompromised patients received TCAD therapy and one patient received OSL monotherapy. All but one patient completed 10 days of TCAD therapy without side effects; one patient receiving TCAD was withdrawn from the study because of respiratory failure and ultimately recovered. Viral load was decreased after TCAD therapy, despite the presence of either AMT- or OSL-resistant virus in two cases. One patient with 2009 influenza A/ H1N1 receiving OSL monotherapy developed confirmed OSL resistance during treatment.

TCAD therapy had similar PKs to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients.

Objective: We aimed to compare the long‐term clinical outcomes of first‐vessel percutaneous coronary intervention (PCI) with drug‐eluting stents (DES) and bare metal stents (BMS) for the treatment of transplant coronary artery disease (TCAD). Background: TCAD is the leading cause of late death in orthotopic heart transplantation (OHT) recipients. PCI is associated with worse clinical outcomes compared with non‐OHT patients. Our institution previously reported superior angiographic outcomes with DES compared with BMS in OHT patients. However, long‐term clinical outcomes comparing PCI with DES versus BMS are lacking. Methods: The data on 105 OHT recipients who underwent first‐vessel PCI with DES (n = 58) or BMS (n = 47) at UCLA Medical Center between 1995 and 2009 were retrospectively analyzed. Results: Five‐year clinical outcomes were not significantly different with DES and BMS in terms of the composite of death, myocardial infarction (MI), or target vessel revascularization (TVR) [(40.8 ± 7.2)% vs. (59.6 ± 7.2)%, log‐rank P = 0.33], death [(31.8 ± 7.8)% vs. (40.4 ± 7.2)%, log‐rank P = 0.46], MI [(12.2 ± 6.2)% vs. (11.3 ± 5.4)%, log rank P = 0.98], TVR [(25.5 ± 6.9)% vs. (26.5 ± 7.3)%, log rank P = 0.76], and time to repeat OHT [(2.27 ± 1.79) vs. (3.22 ± 3.34), P = 0.98]. Conclusions: At long‐term follow‐up, PCI with DES and BMS provided similar clinical outcomes in OHT. Long‐term mortality remains high in OHT recipients after PCI with either DES or BMS. Randomized clinical trials are required to determine the optimal treatment strategy for OHT recipients with TCAD. © 2012 Wiley Periodicals, Inc.