Abstract
Sildenafil is highly effective for treating erectile dysfunction (ED). However, its use has been associated with serious adverse events including myocardial infarctions and strokes, and 130 verifiable plus 112 unverified deaths reported to the US Food and Drug Administration during the 8 months after sildenafil was introduced in the US, and 522 reported deaths during the 13.5 months after its introduction. Moreover, some events have occurred in men taking their first dose of the agent, suggesting that sildenafil, like some drugs that affect blood pressure, may provoke a first-dose reaction. This possibility warrants extra caution to be used when initiating treatment with sildenafil. Such caution is not currently provided by the current dosage guidelines that, for example, recommend the use of sildenafil 50mg initially for most men between the ages of 18 and 65 years, despite wide differences in bodyweight, age, drug metabolism, health status and usage of other medications.
It can be difficult to identify the patient who may be unusually sensitive to the effects of sildenafil. Exercise stress tests have been recommended, but serious adverse events have occurred in men with normal stress tests following the ingestion of sildenafil. Blood pressure monitoring following sildenafil administration will not prevent a serious adverse drug event already in progress. This article discusses the advantages and disadvantages of initiating treatment with a low test dose of sildenafil, performed at home or in the doctor’s office. The advantages of this approach include: (i) identifying patients who are highly sensitive to the effects of sildenafil and who may need no higher dose; (ii) minimising adverse effects such as flushing and dizziness that often frighten patients and may affect adherence; (iii) avoidance of major adverse events; and (iv) reassuring patients with ED who remain wary about trying sildenafil therapy.
Similar content being viewed by others
References
Goldstein I, Lue TF, Padma-Nathan H, et al. Oral sildenafil in the treatment of erectile dysfunction: Sildenafil Study Group. N Engl J Med 1998; 338(20): 1397–404
Boolell M, Gepi-Attee S, Gingell JC, et al. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 1996; 78(2): 257–61
Jarow JP, Burnett AL, Geringer AM. Clinical efficacy of sildenafil citrate based on etiology and response to prior treatment. J Urol 1999; 162(3 Pt 1): 722–5
Langtry HD, Markham A. Sildenafil: a review of its use in erectile dysfunction. Drugs 1999; 57(6): 967–89
Giuliano F, Hultling C, El Masry WS, et al. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury: Sildenafil Study Group. Ann Neurol 1999; 46(1): 15–21
Dinsmore WW, Hodges M, Hargreaves C, et al. Sildenafil citrate (Viagra) in erectile dysfunction: near normalization in men with broad-spectrum erectile dysfunction compared with age-matched healthy control subjects. Urology 1999; 53(4): 800–5
Montorsi F, McDermott TE, Morgan R, et al. Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies. Urology 1999; 53(5): 1011–8
Food and Drug Administration. Postmarketing safety of sildenafil citrate (Viagra): summary of reports of death in Viagra users received from marketing (late March) through mid-November 1998 online. Available from: URL: http://www.fda.gov/-cder/consumerinfo/viagra/safety3.htm. [Accessed 2000 Jun 6]
Siegel-Itzkovich J. Israel bans import of sildenafil citrate after six deaths in the US. BMJ 1998; 316(7145): 1625
Azarbal B, Mirocha J, Shah PK et al. Adverse cardiovascular events associated with the use of Viagra [abstract]. J Am Coll Cardiol 2000; 35Suppl. A: A553–A554
Feenstra J, van Drie-Pierik RJ, Lacle CF, et al. Acute myocardial infarction associated with sildenafil. Lancet 1998; 352(9132): 957–8
Donahue SP, Taylor RJ. Pupil-sparing third nerve palsy associated with sildenafil citrate (Viagra). Am J Ophthalmol 1998 Sep; 126(3): 476–7
Arora RR, Timoney M, Melilli L. Acute myocardial infarction after the use of sildenafil [letter]. N Engl J Med 1999 Aug 26; 341(9): 700
Physicians’desk reference. 53rd ed. Montvale (NJ):Medical Economics Company, 1999
Drug facts and comparisons. St Louis (MO): Facts and Comparisons, 1996
Webster J. Angiotensin converting enzyme inhibitors in the clinic: first-dose hypotension. J Hypertens Suppl 1987 Aug; 5(3): S27–30
Mullen PJ. Unexpected first dose hypotensive reaction to enalapril. Postgrad Med J 1990 Dec; 66(782): 1087–8
Postma CT, Dennesen PJ, de Boo T, et al. First dose hypotension after captopril; can it be predicted? A study of 240 patients. J Hum Hypertens 1992 Jun; 6(3): 205–9
Lin MS, Hsieh WJ. Prazosin-induced first-dose phenomenon possibly associated with hemorrhagic stroke: a report of three cases. Drug Intell Clin Pharmacy 1987 Sep; 21(9): 723–6
Montoliu J, Botey A, Darnell A, et al. Prolonged hypotension after the first dose of atenolol [abstract]. Med Clin 1981 Apr 25; 76(8): 365–6
Melmon K, Morrelli H, Hoffman B, et al., editors. Melmon and Morrelli’s clinical pharmacology, basic principles in therapeutics. 3rd ed. New York (NY): McGraw-Hill, Inc., 1992
Gilman AG, Rall TW, Nies AS, et al. Goodman and Gilman’s the pharmacological basis of therapeutics. New York (NY): Pergamon Press, 1996
Cullen DJ, Bates DW, Small SD, et al. The incident reporting system does not detect adverse drug events: a problem for quality improvement. Joint Commission J Qual Improvement 1995 Oct; 21(10): 541–8
Pfizer/US Pharmaceuticals. Viagra® package insert. 1998 Nov: 1–2 New York (NY)
Murray L, Squire IB, Reid JL, et al. Determinants of the blood pressure response to the first dose of ACE inhibitor in mild to moderate congestive heart failure. Br J Clin Pharmacol 1998 Jun; 45(6): 559–66
Schwartz I, McCarthy D. Sildenafil in the treatment of erectile dysfunction. N Engl J Med 1998; 339: 699–700
Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol 1999 Sep; 84(5B): 11N–7N
Murray L, Squire IB, Reid JL, et al. Determinants of the blood pressure response to the first does of ace inhibitor in mild to moderate congestive heart failure. Br J Clin Pharmacol 1998; 45(6): 559–66
Price DE, Gingell JC, Gepi-Attee S, et al. Sildenafil: study of a novel oral treatment for erectile dysfunction in diabetic men. Diabet Med 1998; 15(10): 821–5
Padma-Nathan H, Steers WD, Wicker PA. Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients: Sildenafil Study Group. Int J Clin Pract 1998; 52(6): 375–9
Shapiro SS, Diem K. The effects of ibuprofen in the treatment of dysmenorrhea. Curr The Res 1981; 30(3): 327–4
Peck C, Barr W, Benet L, et al. Opportunities for integrating of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development. J Clin Pharmacol, 1994; 34: 111–9
Cheitlin MD, Hutter Jr AM, Brindis RG, et al. ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease: American College of Cardiology/American Heart Association. J Am Coll Cardiol 1999; 33(1): 273–82
Johnson MD, Newkirk G, White JR. Clinically significant drug interactions. Postgrad Med 1999; 105: 193–222
Hayashi K, Minezaki KK, Narukawa M, et al. Atrial fibrillation and continuous hypotension induced by sildenafil in an intermittent WPW syndrome patient. Jpn Heart J 1999; 40: 827–30
Kaplan SA, Reis RB, Kohn IJ, et al. Safety and efficacy of sildenafil in postmenopausal women with sexual dysfunction. Urology 1999 Mar; 53(3): 481–6
Nurnberg HG, Lauriello J, Hensley PL, et al. Sildenafil for iatrogenic serotonergic antidepressant medication-induced sexual dysfunction in 4 patients. J Clin Psychiatry 1999; 60(1): 33–5
Nurnberg HG, Hensley PL, Lauriello J, et al. Sildenafil for women patients with antidepressant-induced sexual dysfunction. Psychiatr Serv 1999; 50(8): 1076–8
Balon R. Fluvoxamine-induced erectile dysfunction responding to sildenafil. J Sex Marital Ther 1998 Oct-Dec; 24(4): 313–7
Kaplan B, Ben-Raphael Z, Peled Y, et al. Oral sildenafil may reverse secondary ejaculatory dysfunction during infertility treatment. Fertil Steril 1999; 72(6): 1144–5
Sheehan DV, Hartnett-Sheehan K. The role of SSRIs in panic disorder. J Clin Psychiatry 1996; 517(10 Suppl.): 51–8
McQuay HJ, Carroll D, Glynn CJ. Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia 1993; 48(4): 281–5
Sussman N, Stimmel G. New dosing strategies for psychotropic drugs. Prim Psychiatry 1997; 4(7): 24–30
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cohen, J.S. Should Patients be Given an Initial Low Test Dose of Sildenafil?. Drug-Safety 23, 1–9 (2000). https://doi.org/10.2165/00002018-200023010-00001
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-200023010-00001