Abstract
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:
| Drug . | SONAR finding . | Confirmation . | Peak at risk per year . | #pts/deaths . | % of ADR reports in the FDA database . | FDA Response . | Market 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| Sinusoidal-obstructive syndrome- Leukemia Research 2007 | Biopsy findings | 50,000 | 93/67 | 100% | Black Box | Drug Withdrawn |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 |
| Drug . | SONAR finding . | Confirmation . | Peak at risk per year . | #pts/deaths . | % of ADR reports in the FDA database . | FDA Response . | Market 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 |
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.
Author notes
*
Asterisk with author names denotes non-ASH members.
© 2011 by The American Society of Hematology
2011
