As with all medical products, healthcare professionals are strongly encouraged to report any serious adverse events that are associated with the use of Viagra (sildenafil citrate) to either FDA's MedWatch program by phone (1-800-FDA-1088), fax (1-800-FDA-0178) or mail (using postage-paid form) to FDA, HF-2, 5600 Fishers Lane, Rockville, MD 20852-9787, or to Pfizer Inc. (1-800-438-1985).
May 1998
Dear Doctor,
I am writing to you both as the Medical director for the Sexual Health Team of the U.S. Pharmaceuticals Division of Pfizer Inc. and as a former practicing and board Certified Emergency Physician. As you may be aware, Viagra (sildenafil citrate), the cGMP-specific type 5 phosphodiesterase (PDE5) inhibitor discovered and developed by Pfizer, has recently received FDA approval for the treatment of male erectile dysfunction. You may also be aware, per the enclosed package insert, that the only contraindication for taking Viagra is the concomitant administration of an organic nitrate. We are aware that it is possible that the inadvertent combination of these agents with Viagra may occur and could involve evaluation and treatment of such patients by Emergency Physicians and/or pre-hospital emergency personnel (paramedics/EMTs). Because we would not expect Emergency Physicians to routinely be receiving information about this drug (based on its indication) and in response to several inquiries that we have received on this subject. I felt that it was important for the safety of patients taking Viagra that I write this letter to all Emergency Physicians.
In addition to the approved package insert, I have enclosed a document entitled "Nitric Oxide and Blood Pressure Control" that will provide you with additional information on this subject. Please read it carefully and share it with any of your colleagues who may not be aware of it. This explains the physiologic mechanism underlying the contraindication, which is based on data from several double-blind, placebo controlled interaction studies done with either sublingual nitroglycerin or isosorbide mononitrate in which large and sudden drops in systemic blood pressure occurred in the majority of patients taking Viagra. A list of commonly prescribed short- and long-acting nitrates available in the United States is also included.
It is well documented that sexual activity generally involves an increase in cardiac work and myocardial oxygen demand. Per our package insert [see PRECAUTIONS: GENERAL] for this reason, we are advising physicians to consider the cardiac status of patients for whom they are planning to prescribe Viagra and, in particular, NOT to prescribe it to patients who take organic nitrates in any form, regardless of frequency. We have thought of several possible scenarios in which Emergency Physicians need to be aware of this interaction in order to make appropriate diagnosis and treatment decisions. Those we have considered include:
In addition, although Viagra is only FDA approved for the treatment of male erectile dysfunction, we are aware that women have started taking it, either on their own or via an off-label prescription from a physician. Therefore, although the scenarios described above would be more likely to occur in men, is such off-label use continues, they could also occur in women.
I hope that the information provided here will be helpful to you with patients you encounter who may be taking Viagra. If you would like additional information about Viagra, please contact Pfizer's Medical Information Department at 1-800-438-1985 or visit our Viagra website at www.viagra.com. I thank you for your attention to this important matter.
Sincerely,
Richard L. Siegal, M.D.
Medical Director
Sexual Health
U.S. Pharmaceuticals
Pfizer Inc.
235 East 42nd Street
New York, NY 10017
Nitric Oxide and blood pressure control
Low levels of circulating NO (mainly from endothelium) |
Y Y |
Small local vasodilator effect on resistance vessels |
Y Y |
Minor reduction in blood pressure |
Low levels of circulating NO (mainly from endothelium) |
Y Y |
Potentiation of local vasodilator effect on resistance vessels |
Y Y |
Mild reductions in blood pressure |
Exogenous nitrate |
Y Y |
High levels of circulating NO |
Y Y |
Vasodilator effect of NO on resistance vessels potentiated by sildenafil |
Y Y |
Clinically significant lowering of BP |
Combination of sildenafil and non-nitrate vasodilators
The potentiating effect of sildenafil on lowering of blood pressure in patients taking nitrate therapy is not observed with other vasodilator agents. Extensive safety data from phase II/III studies suggest that patients who take anti-hypertensive medication are not at higher risk of developing symptoms associated with lowering of blood pressure (e.g., dizziness) when they take sildenafil. This applies to patients who take calcium channel blockers, ACE inhibitors, a-blockers, b-blockers, diuretics as single or combined therapy for hypertension and/or angina.
LIST OF REPRESENTATIVE ORGANIC NITRATES
Nitroglycerin
Deponit
Minitran
Nitrek
Nitro-Bid
Nitrocine
Nitro-Derm
Nitro Disc
Nitro-Dur
Nitrogard
Nitroglycerin
Nitroglycerin T/R
Nitroglyn
Nitrol Ointment
Nitrolan
Nitrolingual Spray
Nitrong
Nitropar
Nitropress
Nitroprex
Nitro S.A.
Nitrospan
Nitrostat
Nitro-Trans System
Nitro Transdermal
Nitro-Time
Transderm-Nitro
Tridil
Isosorbide Mononitrate
ISMO
Isosorbide Mononitrate
Monoket
Isosorbide Nitrate