FDA NOTE TO CORRESPONDENTS
For Immediate Release: Aug. 4, 2009
Media Inquiries: Office of Public Affairs, 301-796-4540
Consumer Inquiries: 888-INFO-FDA
Consumer Inquiries: 888-INFO-FDA
FDA: Cancer Warnings Required for TNF Blockers
The U.S. Food and Drug Administration is requiring stronger warnings in the prescribing information for a class of drugs known as TNF blockers. The warnings, which include an updated boxed warning, highlight the increased risk of cancer in children and adolescents who receive these drugs to treat juvenile rheumatoid arthritis, the inflammatory bowel disorder, Crohn’s disease, and other inflammatory diseases.
In addition, the FDA is working with manufacturers to explore new ways to further define the risk of cancer in children and adolescents who use these drugs.
TNF blockers target and neutralize tumor necrosis factor-alpha (TNF-α), a protein that, when overproduced in the body due to chronic inflammatory diseases, can cause inflammation and damage to bones, cartilage and tissue. The drugs in this class include Remicade (infliximab), Enbrel (etancercept), Humira (adalimumab), Cimzia (certolizumab pegol) and Simponi (golimumab).
Today’s action is based on the completion of an investigation first announced by the FDA in June 2008. An analysis of U.S. reports of cancer in children and adolescents treated with TNF-blockers showed an increased risk of cancer, occurring after 30 months of treatment on average. About half of the cancers were lymphomas, a type of cancer involving cells of the immune system. Some of the reported cancers were fatal.
Additional required updates to the prescribing information include incorporation of reports of psoriasis associated with the use of TNF blockers. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm175803.htm
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As always, read bottom up.
Return-Path:Received: from pvlbmailgw01.nlm.nih.gov (canit.nlm.nih.gov [130.14.16.1])
Dear Ms. Vinch:
I received your question about Wellbutrin and cancer.
Taken from NLM Hazardous Substances Data Bank for Bupropion Hydrochloride:
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~4TTYNq:1:
“Animal Toxicity Studies:
Non-Human Toxicity Excerpts:
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a lifetime study of rats, there was an increase in nodular proliferative lesions of the liver at doses of 100 mg to 300 mg/kg of body weight ... a day. However, whether such lesions may be precursors of neoplasms of the liver has not been resolved. Similar lesions were not seen in studies with mice given doses of up to 150 mg/kg a day.
[MICROMEDEX Thomson Health Care. USPDI - Drug Information for the Health Care Professional. 22nd ed. Volume 1. MICROMEDEX Thomson Health Care, Greenwood Village, CO. 2002. Content Reviewed and Approved by the U.S. Pharmacopeial Convention, Inc., p. 704] **PEER REVIEWED**”
Taken from NLM DailyMed record for WELLBUTRIN (bupropion hydrochloride) tablet, film coated [GlaxoSmithKline LLC] -
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=60525754-0d2b-4ba4-918a-1c9d3eff89b2:
“13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Lifetime carcinogenicity studies were performed in rats and mice at bupropion doses up to 300 and 150 mg/kg/day, respectively. These doses are approximately 7 and 2 times the MRHD, respectively, on a mg/m2 basis. In the rat study there was an increase in nodular proliferative lesions of the liver at doses of 100 to 300 mg/kg/day (approximately 2 to 7 times the MRHD on a mg/m2 basis); lower doses were not tested. The question of whether or not such lesions may be precursors of neoplasms of the liver is currently unresolved. Similar liver lesions were not seen in the mouse study, and no increase in malignant tumors of the liver and other organs was seen in either study.”
ClinicalTrials.gov has a study about Wellbutrin and cancer. Information is athttp://clinicaltrials.gov/ct2/show/NCT01077596. Contact information for the study sponsor, is on this page.
I searched PubMed® (http://www.ncbi.nlm.nih.gov/pubmed), but I did not find any information on your topic.
You may want to contact the following organizations for more information:
National Cancer Institute
National Institutes of Health
Public Health Service
U.S. Department of Health and Human Services
6116 Executive Boulevard, Suite 300
Bethesda, MD 20892-8322
Telephone:
(800) 422-6237(toll-free)
(301) 496-5615
(800) 332-8615 TTY (toll-free)
(301) 402-0338 (Fax)
Internet Address: http://www.cancer.gov
American Cancer Society
PO Box 22718
Oklahoma City, OK 73123-1718
Telephone:
(800) 227-2345 (toll-free)
(866) 228-4327 TTY (toll-free)
Internet Address: http://www.cancer.org
Sincerely,
C. Burke
Customer Service
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
custserv@nlm.nih.gov
1-888-346-3656 (within US)
301-594-5983 (international)
The National Library of Medicine (NLM), part of the National Institutes of Health (NIH) makes available a variety of health information sources and offers assistance finding and using them. NLM staff are not healthcare professionals and cannot provide personal research services, answer questions about medical cases or offer specific medical advice. You should discuss those issues with your healthcare provider.
[THREAD ID:1-204QG4]
-----Original Message-----
Sent: 3/10/2014 02:43:55 PM
To: cshelp@wrist.nlm.nih.gov
Subject: Question - general information
Per the FOIA (Freedom of Information Act) the NIH is required to release
this information. What are the correlations between patients who have taken
Wellbutrin developing cancer to those who have not, please?
Thank you,
Vicky Vinch
In a message dated 3/10/2014 2:33:31 P.M. Eastern Daylight Time,
cshelp@wrist.nlm.nih.gov writes:
Reply from the U.S. National Library of Medicine (NLM):
Dear Vicky Vinch,
In response to your message about finding published clinical trial results
for studies investigating a correlation between buproprion (Wellbutrin)
and cancer, you may read the NLM FAQ: Clinical Trial results at
http://www.nlm.nih.gov/services/ctresults.html to see a list of resources you can search
for more information.
Trial results are not always publicly available, even after a clinical
trial ends.
Sincerely,
Cathy Sorge, MSLS
NIH Contractor Librarian
National Library of Medicine
custserv@nlm.nih.gov
[THREAD ID:1-204RBE]
------Original Message------
Sent:03/06/2014 21:53:10
To: Custhelp@mail.nlm.nih.gov
Subject: Question - general information
SUBJECT: ClinicalTrials.gov - Question - general information
NAME: Vicky Vinch
GROUP: General Public
FROM: http://clinicaltrials.gov/ct2/help/for-patient
MESSAGE: Can you please tell me the results of any clinical trials
investigating a correlation between Buproprion (Wellbutrin) and cancer? Is there
a greater incidence of cancer rates with patients who have taken Buproprion
long term as opposed to a control group?
Int Immunopharmacol. 2006 Jun;6(6):903-7. Epub 2006 Jan 25.
A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha andinterferon-gamma in mice.
Author information
- 1Centro de Pesquisas Gonçalo Moniz, FIOCRUZ. Rua Waldemar Falcão, 121- Candeal, Salvador, BA, Brazil, 40296-750.
Abstract
In a wide range of human diseases of inflammatory nature like Crohn's disease, pathology is mediated in part by pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF) or interferon-gamma. We show here that a commonly used generic antidepressant bupropion, in wide use worldwide to treat depression in humans for a decade now, profoundly lowers levels of TNF, interferon-gamma, and interleukin-1 beta in vivo, in a mouse lipopolysaccharide (LPS) induced inflammation model. Mice challenged with an otherwise lethal dose of LPS were protected by bupropion and levels of the anti-inflammatory cytokine interleukin-10 were increased. Previous data in rodents and humans indicate antidepressant effects of bupropion are mediated by its weak reuptake inhibition of norepinephrine and dopamine. Concordant with this, TNF suppression by bupropion in our mouse LPS model was largely abrogated by beta-adrenergic or dopamine D1 receptor antagonists but not by a D2 antagonist. TNF synthesis is controlled by an inverse relationship with intracellular cyclic adenosine monophosphate (cAMP) and stimulation of either beta-adrenoreceptors or D1 dopaminergic receptors result in increased cAMP but stimulation of D2 receptors lowers cAMP. We conclude that bupropion may suppress TNF synthesis by mediating increased signaling at beta-adrenoreceptors and D1 receptors, resulting in increased cAMP that inhibits TNF synthesis. Bupropion is well tolerated also in non-psychiatric populations and has less risk with long term use than current anti-inflammatory, immunosuppressive or TNF suppressive treatments such as prednisone, azathioprine, infliximab, or methotrexate. New anti-inflammatory treatments are needed. We believe a new chapter in antiinflammatory, TNF lowering treatment of disease has been opened. Bupropion's use for this in humans should be explored.
- PMID:
- 16644475
- [PubMed - indexed for MEDLINE]
Wellbutrin & TNF Inhibitor
Bupropion May Aid Patients With Inflammatory Bowel Disease
By Roberta Friedman, PhD
NEW ORLEANS, LA -- November 10, 2003 -- A drug for psychiatric conditions may have a new use in treating inflammatory bowel disease if pilot data presented here November 8th at Neuroscience 2003, the Society for Neuroscience 33rd Annual Meeting, bear out in larger trials.
Bupropion lowered levels of tumor necrosis factor (TNF) in 8 patients who were taking bupropion for depression, with 7 entering the normal range for the inflammatory agent. Levels of TNF ranged from 20 to 1250 pg/mL before bupropion, and dropped to 14 to 2 pg/ml afterwards. One patient's levels remained elevated, at 94 pg/mL.
Larger studies are underway, in Crohn's disease, and in other diseases linked with TNF.
Prior publication by the investigators indicated that some patients taking the agent have remission of Crohn's symptoms. Another short paper in press duplicates the finding. Psoriasis apparently also improves with the drug treatment, according to another, recent paper.
"There are a lot of TNF-[related] diseases," said investigator Dr. Eric Altschuler, resident, rehabilitation medicine, Mt. Sinai Medical Center, New York, New York. "Obviously large, randomized trials are needed [to show the effect of bupropion on TNF is real]," said Dr. Altschuler, but, he added, "if this is true, [bupropion] is cheap, safe, and it's easy [to give]. Doctors have a good comfort level [with the drug]."
The investigators speculate that the result with TNF comes about through activation of dopamine, which increases cyclic adenosine monophosphate inside cells, thereby decreasing the manufacture of TNF by macrophages.
Dr. Altschuler is an inventor listed on a patent application for use of bupropion as a TNF-lowering agent, filed by the University of California. He is also an advisor to GlaxoSmithKline.
[Study title: Bupropion (Wellbutrin) Lowers Tumor Necrosis Factor-Alpha (TNF) Levels: Implications for Disease Treatment. Abstract 105.8]
**************
Fri, Mar 7, 2014 4:12 pm
Dear Vicky Vinch:
Thank you for contacting GSK about WELLBUTRIN® (bupropion hydrochloride) and ZYBAN® (bupropion hydrochloride).
You have asked an important question about WELLBUTRIN® (bupropion hydrochloride) and ZYBAN® (bupropion hydrochloride). We encourage you to discuss medical concerns and symptoms with the appropriate healthcare provider. Your healthcare provider is in the best position to answer your question.
If the physician or pharmacist needs additional information on our products, they can call for medical information at 1-877-356-8368.
A copy of the prescribing information for this product is available athttp://us.gsk.com/products/assets/us_wellbutrin_tablets.pdf and http://us.gsk.com/products/assets/us_zyban.pdffor review and discussion with an appropriate healthcare provider.
If you have further questions concerning GSK or our products, please contact our Response Center at 888-825-5249 during our normal business hours, Monday through Friday 8:30 A.M. to 5:30 P.M. (Eastern Time).
This is a send only email address. Please do not reply to this email.
Sincerely,
ANITRA
Response Center Representative
On 03/07/2014, Vicky Vinch wrote:
> In 2009 the FDA required cancer warnings for all TNF Inhibitors. Why is there no warning on Wellbutrin/Buproprion/Zyban, since these medications are in fact TNF Inhibitors?
(more to come)
**************
Fri, Mar 7, 2014 4:12 pm
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Dear Vicky Vinch:
Thank you for contacting GSK about WELLBUTRIN® (bupropion hydrochloride) and ZYBAN® (bupropion hydrochloride).
You have asked an important question about WELLBUTRIN® (bupropion hydrochloride) and ZYBAN® (bupropion hydrochloride). We encourage you to discuss medical concerns and symptoms with the appropriate healthcare provider. Your healthcare provider is in the best position to answer your question.
If the physician or pharmacist needs additional information on our products, they can call for medical information at 1-877-356-8368.
A copy of the prescribing information for this product is available athttp://us.gsk.com/products/assets/us_wellbutrin_tablets.pdf and http://us.gsk.com/products/assets/us_zyban.pdffor review and discussion with an appropriate healthcare provider.
If you have further questions concerning GSK or our products, please contact our Response Center at 888-825-5249 during our normal business hours, Monday through Friday 8:30 A.M. to 5:30 P.M. (Eastern Time).
This is a send only email address. Please do not reply to this email.
Sincerely,
ANITRA
Response Center Representative
On 03/07/2014, Vicky Vinch wrote:
> In 2009 the FDA required cancer warnings for all TNF Inhibitors. Why is there no warning on Wellbutrin/Buproprion/Zyban, since these medications are in fact TNF Inhibitors?
(more to come)
