Sildenafil 100 mg has been shown to decrease sitting blood pressure in healthy patients one to two hours after administration (mean maximum decrease of 8.3/5.3 mm Hg).1 Similar effects have also been seen with 25 and 50 mg doses. As a result, sildenafil should be used with caution when combined with other medications that lower blood pressure.
Some dosages of sildenafil are used as a first line treatment for pulmonary arterial hypertension.2 The FDA does not recommend combination of sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, with other PDE5 inhibitors or other treatments containing sildenafil.1 The safety and efficacy of these combinations have not been studied, but they may further lower blood pressure.
There are no absolute contraindications to the use of sildenafil with most of the commonly used anti-hypertensive medications. However, caution is advised with the co-administration of sildenafil and alpha blockers due to an additive effect on blood pressure.1 The FDA-approved prescription drug label for sildenafil states that a PDE5 inhibitor should be prescribed to patients only after their blood pressure has stabilized on alpha blockers. PDE5 inhibitors should be initiated at the lowest dose (25 mg) in these patients to prevent hypotension. Other factors that may increase the intensity or risk of hypotension are intravascular volume depletion, combined use with other anti-hypertensive drugs, and whether the patient demonstrates hemodynamic instability on alpha blocker therapy alone.
Pfizer’s package insert describes study data on the risk of hypotension with the co-administration of sildenafil and the alpha blocker, doxazosin, in normotensive participants.1 The addition of sildenafil (50 mg) to doxazosin treatment was associated with an additional decline in supine and standing systolic blood pressure of 9.08 and 11.62 mm Hg, respectively, compared to the addition of a placebo to doxazosin treatment (p<0.05). Decrease in blood pressure and adverse reactions were also observed with 25 and 100 mg doses of sildenafil. With higher doses of sildenafil, more patients became hypotensive and experienced adverse reactions, such as vasodilation and lightheadedness. Although the study was conducted with normotensive subjects, it suggests that co-administration of doxazosin with high dose sildenafil may lead to increased incidence of hypotension and adverse effects.
Use of sildenafil with other anti-hypertensive medicines is cautioned due to the possible additive effect on blood pressure.1 This was demonstrated in a randomized, placebo-controlled drug interaction study of sildenafil and amlodipine.3 Amlodipine (5 mg or 10 mg) lowered blood pressure by 8.8/1.6 mm Hg (systolic/diastolic) in the placebo group and by 16.8/8.4 mm Hg when administered with sildenafil.
However, several other randomized, double-blind, placebo-controlled studies have concluded that the combination of sildenafil and anti-hypertensive medications is safe.4-6 There were no additional adverse events in the treatment groups compared to placebo or control groups in these studies.4-6 For example, Vardi et al. studied the effect of sildenafil on blood pressure in hypertensive (n=22) and normotensive (n=27) men.7 The hypertensive group continued their treatment of alpha blockers (n=10), calcium-channel antagonists (n=8), and angiotensin-converting enzyme inhibitors (n=7). Twelve of these men were taking only one anti-hypertensive and 10 men were taking two or more. For both normotensive and hypertensive groups, blood pressure was measured at baseline and after the administration of sildenafil (100 mg). Sildenafil lowered the mean blood pressure by 8.5/5.7 mm Hg (systolic/diastolic) in hypertensives and 3.7/3.6 mm Hg in normotensives. The decrease in blood pressures from baseline was neither significant within each group nor between groups.
The safety and efficacy trials of sildenafil were not conducted in men with uncontrolled hypertension (blood pressure over 170/110 mm Hg).1 Therefore, the FDA cautions the use of sildenafil in this population.
The use of sildenafil citrate with nitrates is contraindicated because the combination potentiates the hypotensive effect of nitrates.1 Although nitrates are not used as a daily anti-hypertensive, patients who have hypertension may take nitrates for angina.8 Patients with heart failure with reduced ejection fraction may also take nitrates to reduce pulmonary congestion and improve exercise tolerance.9 To investigate the drug interaction between sildenafil and nitrates, Webb et al. conducted a randomized, double-blind, placebo-controlled, two-way crossover study with 12 healthy men.3 Administration of a sublingual glyceral trinitrate tablet (500 μg) caused a four-fold decrease in systolic blood pressure compared to placebo when administered with sildenafil.
References
- Viagra [package insert]. New York, NY: Pfizer, Inc.; 2017.
- McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: A report of the american college of cardiology foundation task force on expert consensus documents and the american heart association <em>developed in collaboration with the american college of chest physicians; american thoracic society, inc.; and the pulmonary hypertension association. Circulation. 2009;53(17):1573-1619.
- Webb DJ, Freestone S, Allen MJ, Muirhead GJ. Sildenafil citrate and blood-pressure–lowering drugs: Results of drug interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol. 1999;83(5, Supplement 1):21-28.
- Kloner RA, Brown M, Prisant LM, Collins M. Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy. Sildenafil study group. Am J Hypertens. 2001;14(1):70-73.
- Pickering TG, Shepherd AMM, Puddey I, et al. Sildenafil citrate for erectile dysfunction in men receiving multiple antihypertensive agents*a randomized controlled trial. Am J Hypertens. 2004;17(12):1135-1142.
- Zusman RM, Prisant LM, Brown MJ. Effect of sildenafil citrate on blood pressure and heart rate in men with erectile dysfunction taking concomitant antihypertensive medication. Sildenafil study group. J Hypertens. 2000;18(12):1865-1869.
- Vardi Y, Klein L, Nassar S, Sprecher E, Gruenwald I. Effects of sildenafil citrate (viagra) on blood pressure in normotensive and hypertensive men. Urology. 2002;59(5):747-752.
- Nitrostat [package insert]. New York, New York: Pfizer Inc.; 2018.
- Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/hfsa focused update of the 2013 ACCF/AHA guideline for the management of heart failure: A report of the american college of cardiology/american heart association task force on clinical practice guidelines and the heart failure society of america. Circulation. 2017.
