ISIS Press Release 10/04/06

Warnings on FDA Approved Monoclonal Antibody Drugs

Prof. Joe Cummins

This is a compilation of safety information on monoclonal antibody drugs already approved by the US FDA (Food and Drug Administration), most of them posted on the FDA website. The URLs are included at the time of compilation (23 March 2006).

1. Orthoclone OKT 3 mouse monoclonal antibody, Ortho Biotech, Transplant anti-rejection

Safety information:  Anaphylactic or anaphylactoid reactions may occur following administration of any dose or course of ORTHOCLONE OKT3. In addition, serious, occasionally life-threatening or lethal, systemic, cardiovascular, and central nervous system reactions have been reported following administration of ORTHOCLONE OKT3. These have included: pulmonary edema, especially in patients with volume overload; shock, cardiovascular collapse, cardiac or respiratory arrest, seizures, coma, cerebral edema, cerebral herniation, blindness and paralysis. http://www.orthobiotech.com/orthoclone.html

2. ReoPro  humanized mouse  monoclonal antibody Centocor, prevents blood clotting

Side effects: Acid or sour stomach; belching; burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings; changes in vision; delusions; dementia; fear; heartburn; indigestion or stomach discomfort, upset or pain; mood or mental changes; nausea; nervousness; vomiting. http://www.drugs.com/cons/ReoPro.html

3. Rituxan (Rituximab) humanized mouse monoclonal antibody Genetech, treatment of Non-Hodgkins lymphoma

Warning: Fatal Infusion Reactions: Deaths within 24 hours of RITUXAN infusion have been reported. These fatal reactions followed an infusion reaction complex which included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrilation orcardiogenic shock. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. http://www.fda.gov/medwatch/SAFETY/2005/Jan_PI/Rituxan_PI.pdf

4. Zenapax (daclizumab) humanized mouse monoclonal antibody, Hoffman-La Roche,  transplant immune suppression

Warning: Severe, acute (onset within 24 hours) hypersensitivity reactions including anaphylaxis have been observed both on initial exposure to ZENAPAX and following re-exposure. These reactions may include hypotension, bronchospasms, wheezing, laryngeal edema, pulmonary edema, cyanosis, hypoxia, respiratory arrest, cardiac arrhythmia, cardiac arrest, peripheral edema, loss of consciousness, fever, rash, urticaria, diaphoresis, pruritus, and/or injection site reactions. http://www.fda.gov/medwatch/SAFETY/2003/zenapax.htm

5. Simulect humanized mouse monoclonal antibody, Novartis transplant ant-rejection

Warning: severe acute (onset within 24 hours) hypersensitivity reactions including anaphylaxis have been observed both on initial exposure to Simulect® and/or following re-exposure after several months. These reactions may include hypotension, tachycardia, cardiac failure, dyspnea, wheezing, bronchospasm, pulmonary edema, respiratory failure, urticaria, rash, pruritus, and/or sneezing. If a severe hypersensitivity reaction occurs, therapy with Simulect® should be permanently discontinued. Medications for the treatment of severe hypersensitivity reactions including anaphylaxis should be available for immediate use. Patients previously administered Simulect® should only be re-exposed to a subsequent course of therapy with extreme caution. http://www.fda.gov/medwatch/safety/2000/simule.htm

6. Synagis  humanized mouse monoclonal antibody, Medimmune,  anti-respiratory syncytial virus 

Warning: Very rare cases of anaphylaxis (<1 case per 100,000 patients) have been reported following re-exposure to Synagis (palivizumab) [see Adverse Reactions, Post-Marketing Experience]. Rare severe acute hypersensitivity reactions have also been reported on initial exposure or re-exposure to palivizumab. http://www.fda.gov/medwatch/SAFETY/2002/Synagis_PI.pdf

7. Remicade,  humanized mouse monoclonal antibody, Centocor anti-arthritis

Warning; tuberculosis infection some fatal http://www.fda.gov/medwatch/safety/2005/Sep_PI/Remicade_PI.pdf

8. Herceptin (Trastuzumab) humanized mouse monoclonal antibody, Genetech cancer therapy

Warning: CARDIOMYOPATHY: HERCEPTIN administration can result in the development of ventricular dysfunction and congestive heart failure. http://www.accessdata.fda.gov/scripts/cder/onctools/labels.cfm?GN=Trastuzumab

9. Mylotarg humanized mouse monoclonal antibody,Wyeth, cancer therapy

Warning: Mylotarg administration can result in severe hypersensitivity reactions (including anaphylaxis), and other infusion-related reactions which may include severe pulmonary events. Infrequently, hypersensitivity reactions and pulmonary events have been fatal http://www.fda.gov/medwatch/SAFETY/2004/apr_PI/Mylotarg_PI.pdf

10. Campath-1H (Alemtuzumab) humanized mouse monoclonal antibody, Genzym leukemia cancer treatment 

Warning: Campath may lower the ability of the bone marrow to make blood cells. Some of these effects can be severe and lead to death. Three patients in a clinical study of the drug Campath for the treatment of Multiple Sclerosis (MS) developed severe idiopathic thrombocytopenic purpura (ITP). http://www.fda.gov/cder/drug/InfoSheets/patient/alemtuzumabPIS.pdf

11. Zevalin Mouse monoclonal antibody, Biogen Idec cancer therapy (Yttrium  radio therapy associated)

Warning: Deaths have occurred within 24 hours of Rituximab infusion, an essential component of the ZEVALIN therapeutic regimen. These fatalities were associated with an infusion reaction symptom complex that included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. http://www.accessdata.fda.gov/scripts/cder/onctools/labels.cfm?GN=Ibritumomab%20Tiuxetan

12. Humira Human monoclonal antibody, Abott  arthritis treatment

Warning: TUBERCULOSIS (FREQUENTLY DISSEMINATED OR EXTRAPULMONARY AT CLINICAL PRESENTATION), INVASIVE FUNGAL INFECTIONS, AND OTHER OPPORTUNISTIC INFECTIONS, HAVE BEEN OBSERVED IN PATIENTS RECEIVING HUMIRA. SOME OF THESE INFECTIONS HAVE  BEEN FATAL  http://www.fda.gov/medwatch/safety/2005/Oct_PI/Humira_PI.pdf

13. Xolair humanized mouse monoclonal antibody, Genetech treatment of allergic asthma

 Warning: more patients treated with Xolair developed a new or recurrent cancer compared to control patients. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/printer.cfm?id=153

14. Bexxar (Tositumomab and Iodine I 131) mouse monoclonal antibody Corixa company, cancer therapy 

Warning: Hypersensitivity reactions, including anaphylaxis.  http://www.fda.gov/cder/foi/label/2003/tosicor062703LB.pdf

15. Raptiva humanized mouse monoclonal antibody, Genetech, treatment of psoriasis

Warning: Hemolytic anemia; serious infections has been updated to include rare postmarketing reports of necrotizing fasciitis, tuberculous pneumonia, bacterial sepsis with seeding of distant sites, severe pneumonia with neutropenia, and worsening of infection (e.g. cellulitis,pneumonia) despite antimicrobial treatment. http://www.fda.gov/medwatch/safety/2005/raptiva_deardoc_071205.pdf

16. Erbitux humanized mouse monoclonal antibody, Imclone systems, cancer therapy

Warning: Severe infusion reactions occurred with the administration of ERBITUX in approximately 3% of patients, rarely with fatal outcome (<1 in 1000). Severe infusion reactions are characterized by rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), urticaria, and hypotension. http://www.fda.gov/medwatch/safety/2005/Sep_PI/Erbitux_PI.pdf

17. Avastin humanized mouse monoclonal antibody Genetech, cancer therapy 

Warning: AVASTIN administration can result in the development of gastrointestinal perforation and wound dehiscence, in some instances resulting in fatality. Gastrointestinal perforation, sometimes associated with intra-abdominal abscess, occurred throughout treatment with AVASTIN. Serious, and in some cases fatal, hemoptysis has occurred in patients with non–small cell lung cancer treated with chemotherapy and AVASTIN. http://www.fda.gov/cder/foi/label/2004/125085lbl.pdf

18. Tsabri humanized mouse monoclonal antibody, Biogen Idec, treatment of multiple sclerosis (MS)

Suspended Marketing of Tysabri (natalizumab) 2005:  FDA is issuing this public health advisory to inform patients and health care providers about the suspended marketing of Tysabri (natalizumab) due to two serious adverse events reported with its use. FDA has received a report from Biogen Idec, the manufacturer of Tysabri, of one confirmed, fatal case and one additional case of progressive multifocal leukoencephalopathy (PML) in patients receiving Tysabri for multiple sclerosis (MS). Both patients were enrolled in a long-term clinical trial and had been taking Tysabri for more than two years. http://www.fda.gov/cder/drug/advisory/natalizumab.htm

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