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Sildenafil and Nonnitrate Antihypertensive Medications

Jay S. Cohen, MD
[+] Author Affiliations

Phil B. Fontanarosa, MDDeputy Editor: IndividualAuthor
Margaret A. Winker, MDDeputy Editor: IndividualAuthor
Stephen J. Lurie, MD, PhDFishbein Fellow: IndividualAuthor

Copyright 2000 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

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JAMA. 2000;283(2):201-202. doi:10-1001/pubs.JAMA-ISSN-0098-7484-283-2-jbk0112
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To the Editor: The vasodilatory properties of sildenafil (Viagra) are well established and many of sildenafil's adverse effects (headache, flushing, dyspepsia, dizziness) result from vasodilation. Sildenafil-related myocardial infarction and sudden death also may be related to its vasodilatory effects.

Sildenafil alone has been associated with episodes of hypotension and the concomitant use of sildenafil and nitrate vasodilators is contraindicated because of hypotensive crises. Thus, there is some question whether the use of sildenafil in patients taking nonnitrate antihypertensive drugs might present an increased risk. Certainly, many antihypertensive drugs alone cause vasodilation and hypotension. According to the package insert, "Controlled studies of drug interactions between Viagra and other antihypertensive medications [except amlodipine] have not been performed."1 It would be helpful for clinicians to know the results of a study involving sildenafil and, for example, doxazosin mesylate or terazosin hydrochloride, which are well known to cause hypotensive reactions in some patients.

To determine whether current data might indicate an increased risk among patients taking sildenafil in combination with nonnitrate antihypertensives, I requested, in December 1998, the case reports of sildenafil-related adverse drug reactions (ADRs) that had been submitted to the US Food and Drug Administration (FDA). I received the list of ADR reports from April to June 28, 1998.2 The list contained 439 ADRs. Of these, 127 (29%) occurred in patients taking antihypertensive drugs. Twenty of these cases involved nitrates. Removing these cases, 107 (25.5%) of the remaining 419 reports involved other antihypertensive drugs. However, the FDA list contained many apparent redundancies and often lacked key information such as patients' ages or details of adverse events. Removing the redundancies, 360 cases remained. Of these, 87 patients (24.2%) were taking nonnitrate antihypertensive drugs.

Thus, overall, about 24% of sildenafil-related ADRs reported to the FDA from April 22, through June 28, 1998 occurred in patients taking nonnitrate antihypertensive drugs. This percentage exceeds the approximately 13% of American adults receiving treatment for hypertension,3 but it is less than the 33% of subjects taking antihypertensives in the placebo-controlled sildenafil trials.4 Whether the fact that nearly one quarter of sildenafil reports to the FDA also involved antihypertensive drugs indicates an increased risk factor, a reporting bias, a statistical error secondary to incomplete information in the FDA reports, or a reflection of an older and less healthy patient population taking sildenafil is not known.

Physicians should be aware of the possibility of hypotensive reactions in patients taking antihypertensive drugs and sildenafil and should alert patients about this potential adverse effect.5

REFERENCES

 Viagra [package insert]. New York, NY: Pfizer Inc; November 1998.
US Food and Drug Administration,  FDA: Adverse Event Reporting System (AERS), Freedom of Information Report. Washington, DC: Dept of Health and Human Services; August 3, 1998.
Burt  VL, Whelton  P, Roccella  EJ.  et al.  Prevalence of hypertension in the US adult population: results from the the third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305-313.
Morales  A, Gingell  C, Collins  M, Wicker  PA, Osterloh  IH. Clincal safety of oral sildenafil (Viagra) in the treatment of erectile dysfunction. Int J Impot Res. 1998;10:69-74.
Cheitlin  MD, Hutter Jr  AM, Bridis  RG.  et al.  Use of sildenafil (Viagra) in patients with cardiovascular disease. J Am Coll Cardiol. 1999;33:273-282.

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 Viagra [package insert]. New York, NY: Pfizer Inc; November 1998.
US Food and Drug Administration,  FDA: Adverse Event Reporting System (AERS), Freedom of Information Report. Washington, DC: Dept of Health and Human Services; August 3, 1998.
Burt  VL, Whelton  P, Roccella  EJ.  et al.  Prevalence of hypertension in the US adult population: results from the the third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305-313.
Morales  A, Gingell  C, Collins  M, Wicker  PA, Osterloh  IH. Clincal safety of oral sildenafil (Viagra) in the treatment of erectile dysfunction. Int J Impot Res. 1998;10:69-74.
Cheitlin  MD, Hutter Jr  AM, Bridis  RG.  et al.  Use of sildenafil (Viagra) in patients with cardiovascular disease. J Am Coll Cardiol. 1999;33:273-282.
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