Abstract 4756

Introduction:

SONAR, the only state-funded (South Carolina) pharmacovigilance initiative in the nation, focuses on identifying near fatal side effects of hematology and oncology therapeutics. Most safety findings are like “trees falling in the forest” – with no one hearing the noise. Our objective was to describe the outcomes from the findings of the pharmacovigilance efforts from the SONAR group.

Methods:

SONAR investigators reviewed practice and policy outcomes to our identification of adverse drug reactions with hematologic implications. Data sources used were PubMed, the Food and Drud Administration (FDA) files, and the Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).

Results:
DrugSONAR findingConfirmationPeak at risk per year#pts/deaths% of ADR reports in the FDA databaseFDA ResponseMarket Action
Gemtuzumab for AML patients Sinusoidal-obstructive syndrome- Leukemia Research 2007 Biopsy findings 50,000 93/67 100% Black Box Drug Withdrawn 
Ticlopidine, clopidogrel, prasugrel (antiplatelet agents) Thrombotic Thrombocytopenic Purpura (TTP)- NEJM 2000, Lancet 1998, JAMA 1998 Antibodies Ticlopidine 1 million, Clopidogrel 5 million Ticlopidine 60/20, clopidogrel 37/5, prasugrel 9/0 60%, 90%, and 100% respectively Black Box, Warnings Ticlopidine market sales < $10 million (despite being generic) 
Rituximab- for lymphoma treatment PML- Blood 2009     Warnings None 
Nevirapine for post-HIV-exposure following exposure to blood products Fulminant hepatitis in HCWs following needle-stick- Ann of Int Med 2002 Biopsy findings  30/0 20% Dear Doctor Drug not used in this setting. CD4 thresholds added for use among HIV-infected individuals. 
Thalidomide, lenalidomide for multiple myeloma patients Venous thromboembolism (VTE)- JAMA 2006  17,000 96/12 71% Warning, Dear Dr VTE prophylaxis is now routine – based on survey data 
Voriconazole for anti-fungal prophylaxis Breakthrough Zygomycoses following stem cell transplantation for hematologic malignancies - BMT 2007     Label change None 
Eprex-formulation of Epoetin Pure red cell aplasia- NEJM 2000 Neutralizing antibodies  208/0 100% Warning, Dear Dr SQ use discontinued 
Epoetin, darbepoetin- cancer pts Mortality, tumor progression- JAMA 2008     Black Box, warning Marked decrease in ESA use- based on survey data 
Megakaryocyte growth and development factor administration to healthy volunteers Lymphoid malignancies - B J of Haematology 2006   13/0 0% None Drug development discontinued 
Granulocyte colony-stimulating factor treated cancer patients Leukemia/MDS - JNCI 2008, B J Haematol 2006     None None 
Gemcitabine Pneumonitis   150/52 100% Label change  
CYPHER stents for coronary artery disease Hypersensitivity at the stent site Autopsy findings 1 million 12/2 43% Dear Doctor  
Enoxaparin – following coronary artery stent procedures Severe hemorrhage and pseudoaneurysm formation Known toxicity  5/0 0% None  
DrugSONAR findingConfirmationPeak at risk per year#pts/deaths% of ADR reports in the FDA databaseFDA ResponseMarket Action
Gemtuzumab for AML patients Sinusoidal-obstructive syndrome- Leukemia Research 2007 Biopsy findings 50,000 93/67 100% Black Box Drug Withdrawn 
Ticlopidine, clopidogrel, prasugrel (antiplatelet agents) Thrombotic Thrombocytopenic Purpura (TTP)- NEJM 2000, Lancet 1998, JAMA 1998 Antibodies Ticlopidine 1 million, Clopidogrel 5 million Ticlopidine 60/20, clopidogrel 37/5, prasugrel 9/0 60%, 90%, and 100% respectively Black Box, Warnings Ticlopidine market sales < $10 million (despite being generic) 
Rituximab- for lymphoma treatment PML- Blood 2009     Warnings None 
Nevirapine for post-HIV-exposure following exposure to blood products Fulminant hepatitis in HCWs following needle-stick- Ann of Int Med 2002 Biopsy findings  30/0 20% Dear Doctor Drug not used in this setting. CD4 thresholds added for use among HIV-infected individuals. 
Thalidomide, lenalidomide for multiple myeloma patients Venous thromboembolism (VTE)- JAMA 2006  17,000 96/12 71% Warning, Dear Dr VTE prophylaxis is now routine – based on survey data 
Voriconazole for anti-fungal prophylaxis Breakthrough Zygomycoses following stem cell transplantation for hematologic malignancies - BMT 2007     Label change None 
Eprex-formulation of Epoetin Pure red cell aplasia- NEJM 2000 Neutralizing antibodies  208/0 100% Warning, Dear Dr SQ use discontinued 
Epoetin, darbepoetin- cancer pts Mortality, tumor progression- JAMA 2008     Black Box, warning Marked decrease in ESA use- based on survey data 
Megakaryocyte growth and development factor administration to healthy volunteers Lymphoid malignancies - B J of Haematology 2006   13/0 0% None Drug development discontinued 
Granulocyte colony-stimulating factor treated cancer patients Leukemia/MDS - JNCI 2008, B J Haematol 2006     None None 
Gemcitabine Pneumonitis   150/52 100% Label change  
CYPHER stents for coronary artery disease Hypersensitivity at the stent site Autopsy findings 1 million 12/2 43% Dear Doctor  
Enoxaparin – following coronary artery stent procedures Severe hemorrhage and pseudoaneurysm formation Known toxicity  5/0 0% None  
View Large
Conclusions:

Most SONAR findings have been followed by FDA notifications and market responses. Identifying and reporting sADRs can have marked beneficial effects on medical care.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
adverse effects, pharmacovigilance, translating, stick dosage form, ticlopidine, clopidogrel, venous thromboembolism, biopsy, cancer, erythropoietin

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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