Updates to the Warnings and Precautions, Pneumonia subsection of the Fuzeon (enfuvirtide) package insert were approved on April 28, 2011 in response to results of a study conducted under a Postmarketing Commitment. Drug sponsor, Roche, submitted the results from an “Observational Cohort Study on the Incidence of Pneumonia in HIV-1 Patients Treated with Fuzeon.” The study was conducted as a result of findings during the initial review of the registrational Phase 3 trials, which showed a relative increase in the incidence of bacterial pneumonia for subjects receiving Fuzeon versus control subjects. The increased pneumonia findings were included in the Warnings and Precautions section of the package insert.
The findings from the study are included in Warnings and Precautions section 5.3 Pneumonia of the package insert as follows. The new text appears below in italics.
5.3 Pneumonia
An increased rate of bacterial pneumonia was observed in subjects treated with FUZEON in the Phase 3 clinical trials compared to the control arm. The incidence of pneumonia was 2.7% or 3.2 events/100 patient-years in subjects receiving FUZEON + background regimen. On analysis of all diagnoses of pneumonia (pneumonia, bacterial pneumonia, bronchopneumonia, and related terms) in T20-301 and T20-302, an increased rate of bacterial pneumonia was observed in subjects treated with FUZEON compared to the control arm (6.9%, 6.7 pneumonia events per 100-patietn-years versus 0.6 events per 100 patient-years, respectively). Approximately half of the study subjects with pneumonia required hospitalization. Three subject deaths in the FUZEON arm were attributed to pneumonia; all three had serious concomitant AIDS-related illnesses that contributed to their deaths. Risk factors for pneumonia included low initial CD4 lymphocyte count, high initial viral load, intravenous drug use, smoking, and a prior history of lung disease.
Because it was unclear whether the higher incidence rate of pneumonia was related to FUZEON use, an observational study in 1850 HIV-infected patients (740 FUZEON treated patients and 1110 non-FUZEON treated patients) was conducted to evaluate the risk of pneumonia in patients treated with FUZEON. A total of 123 patients had a confirmed or probable pneumonia event in this study (62 in the FUZEON treatment arm with 1962 patient-years of observation and 61 in the non-FUZEON treatment arm with 3378 patient-years of observation). The incidence of pneumonia was 3.2 events/100 patient-years in the FUZEON treatment arm and 1.8 events/100 patient-years in the non-FUZEON treatment arm. The hazard ratio, adjusting for other baseline risk factors, was 1.34 (95% C.I. = 0.90 – 2.00). Based on this observational study, it is not possible to exclude an increased risk of pneumonia in patients treated with FUZEON compared to non-FUZEON treated patients.
It is unclear if the increased incidence of pneumonia is related to FUZEON use. However, because of these findings, patients with HIV-1 infection should be carefully monitored for signs and symptoms of pneumonia, especially if they have underlying conditions which may predispose them to pneumonia. Risk factors for pneumonia included low initial CD4 cell count, high initial viral load, intravenous drug use, smoking, and a prior history of lung disease.
The complete revised label will be posted soon at Drugs@FDA
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
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