Sildenafil and Isosorbide Dinitrate: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sildenafil
Isosorbide Dinitrate
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Potentiation of hypotensive effects
Interaction Deep Dive
Regular or intermittent concomitant sildenafil and organic nitrate use is contraindicated as hypotension due to additive effects of increased cyclic guanosine monophosphate (cGMP) levels may occur1. Hypotension lasted 8 vs 4 hours with sildenafil and SL nitroglycerin in men with stable angina vs healthy men 6. Slowly titrated IV nitroglycerin following a single sildenafil dose may be tolerated in men with stable coronary artery disease 5. Avoid nitrates in acute coronary syndrome for at least 24 hours after sildenafil 3 or longer in hepatic or severe renal impairment. Monitor carefully if used after 24 hours. A short-acting IV nitrate with close monitoring may be tolerated 4.
Why it happens (mechanism)
Increased levels of cyclic guanosine monophosphate (cGMP) from sildenafil and nitrates
Literature reports
4 reports — tap to read
a) In a randomized crossover study in men with a history of angina pectoris and stable coronary artery disease (N=34), subjects received a single dose of sildenafil 100 mg or placebo followed 45 minutes later by IV nitroglycerin 5 mcg/minute escalating at 10-minute intervals to 10, 20, 40, 80, 120, and finally 160 mcg/minute. Hypotension that was primarily asymptomatic occurred in 26 patients who received sildenafil compared with 17 who received placebo, which was a significant difference. Most cases of hypotension required discontinuation of the nitroglycerin infusion. Two sildenafil cases were symptomatic. The median maximum tolerated nitroglycerin dose was significantly higher with placebo versus sildenafil (160 mcg/minute vs 80 mcg/minute). Only 25% of the sildenafil-treated patients reached the 160-mcg/minute dose of nitroglycerin compared with 59% of placebo-treated patients. No serious adverse events were reported. Notably, there was large interpatient variability in sildenafil plasma concentration levels following the single dose 5.
b) Two randomized crossover studies found the hypotensive interaction between sildenafil and sublingual nitroglycerin in men with stable angina lasted 8 hours after sildenafil administration, while in healthy male subjects, the hypotensive interaction between sildenafil and sublingual nitroglycerin was confined to 4 hours. Male patients with stable angina (n=20) and healthy male subjects (n=33) were challenged with a single sublingual nitroglycerin 400 mcg spray at 1 hour, 4 hours, 6 hours, and 8 hours after administration of a sildenafil 100 mg oral tablet to determine the time course of the hypotensive interaction between sildenafil and sublingual nitroglycerin. In angina patients, there was a greater mean maximal reduction in BP with sildenafil/nitroglycerin compared to placebo/nitroglycerin for up to 8 hours. The mean differences in maximum systolic BP reduction at 1, 4, 6 and 8 hours were -16 mmHg, -12 mmHg, -6 mmHg, and -9 mmHg, respectively. In healthy men, a significant mean maximal reduction in BP with sildenafil/nitroglycerin compared to placebo/nitroglycerin occurred only 1 hour after sildenafil administration (systolic BP -23.8 mmHg (2.8), diastolic BP -14.9 mmHg (2.3)); versus placebo/nitroglycerin (systolic BP -13.5 mmHg (2.5) diastolic BP -6.9 mmHg (1.2)). Side effects were most commonly reported when nitroglycerin was administered 1 hour after sildenafil, and included symptoms of hypotension, such as dizziness and lightheadedness 6.
c) A randomized, double-blind, placebo-controlled, two-way crossover study of 12 healthy men demonstrated that sildenafil potentiates the hypotensive effects of organic nitrates. The men received either 25 mg sildenafil three times daily or placebo for four days, followed by a single morning dose on day 5. Nitroglycerin was given intravenously on day 4 as a stepwise infusion one hour after the sildenafil morning dose. On day 5, nitroglycerin 500 mcg was given sublingually one hour after the morning dose of sildenafil or placebo. In both cases, the nitroglycerin was discontinued when the subject's systolic blood pressure was decreased by more than 25 mm Hg. For the intravenous infusion, two of the 12 subjects in the placebo group completed the 25-minute infusion, while none completed the infusion in the sildenafil group. Similarly, with sublingual nitroglycerin, four of the 12 subjects in the placebo group removed the sublingual tablet after three to four minutes, versus 11 of 12 subjects who removed the tablet after two to seven minutes in the sildenafil group. The most frequently occurring adverse events reported by the 12 subjects were headache and dizziness 7.
d) Two studies demonstrated the effects of a single oral dose of sildenafil citrate on blood pressure in men taking isosorbide mononitrate and glyceryl trinitrate for stable angina. Sixteen subjects received oral isosorbide mononitrate beginning 5 to 7 days before receiving a single dose of sildenafil or placebo. Administration of isosorbide mononitrate with sildenafil resulted in substantially greater decreases in blood pressure from baseline (-52/-29 mm Hg) as compared with those subjects receiving isosorbide mononitrate plus placebo (-25/-15 mm Hg). The second study involved 15 male subjects who were receiving sublingual nitroglycerin as needed for stable angina. A single dose of sildenafil or placebo followed by nitroglycerin sublingual one hour later was administered to patients. At least seven days later, subjects received the alternate study drug (sildenafil or placebo) and nitroglycerin sublingual one hour later. Sildenafil plus nitroglycerin resulted in an increase in mean reductions from baseline in systolic/diastolic blood pressure (-36/-21 mm Hg) compared with placebo plus nitroglycerin (-26/-12 mm Hg). Substantially greater decreases in blood pressure occur from baseline with administration of isosorbide mononitrate plus sildenafil compared to patients receiving isosorbide mononitrate plus placebo. A clinically significant reduction in blood pressure occurs with concomitant use of sildenafil and nitrates, such as isosorbide mononitrate and nitroglycerin 8.
Common questions
Can I take Sildenafil and Isosorbide Dinitrate together?
Potentiation of hypotensive effects Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sildenafil and Isosorbide Dinitrate interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Sildenafil or Isosorbide Dinitrate need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (8)
- Product Information: REVATIO(R) oral tablets, oral suspension, intravenous injection, sildenafil oral tablets, oral suspension, intravenous injection. Pfizer Labs (per FDA), New York, NY, 2023. DailyMed
- O'Gara PT, Kushner FG, Ascheim DD, et al: 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61(4):e78-e140.
- Amsterdam EA, Wenger NK, Brindis RG, et al: 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130(25):e344-e426.
- Cheitlin MD, Hutter AM, Brindis RG, et al: Use of sildenafil (Viagra) in patients with cardiovascular disease. Technology and Practice Executive Committee. Circulation 1999; 99(1):168-177. PubMed
- Parker JD, Bart BA, Webb DJ, et al: Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: a double-blind, placebo-controlled, randomized, crossover trial. Crit Care Med 2007; 35(8):1863-1868. DOI
- Oliver JJ, Kerr DM, & Webb DJ: Time-dependent interactions of the hypotensive effects of sildenafil citrate and sublingual glyceryl trinitrate. Br J Clin Pharmacol 2009; 67(4):403-412. PubMed
- Webb DJ, Freestone S, Allen MJ, et al: Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol 1999; 83:21C-28C. DOI
- Webb D, Muirhead G, Wulff M, et al: Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patinets with stable angina. J Am Coll Cardiol 2000; 36(1):25-31.
Keep reading about Sildenafil
Keep reading about Isosorbide Dinitrate
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist