Can Nitroglycerin Be Given to a Patient Who Has Taken Sildenafil?

Joanna M. Pangilinan, PharmD, BCOP

Disclosures

June 05, 2009

Question

When a male patient who had taken sildenafil presents with an acute coronary syndrome (ACS), how real is the risk for serious hypotension if nitroglycerin (NTG) is titrated intravenously (IV)?

Response from Joanna Pangilinan, PharmD, BCOP
Pharmacist, Comprehensive Cancer Center, University of Michigan Health System, Ann Arbor, Michigan

The phosphodiesterase-5 (PDE5) inhibitor sildenafil is approved by the US Food and Drug Administration for the treatment of erectile dysfunction.[1] Sildenafil is contraindicated in combination with nitrates due to the risk for a pharmacodynamic drug interaction that can result in severe hypotension[1] and death.[2]

Men with coronary artery disease (CAD), a condition with increased prevalence of erectile dysfunction, may in certain medical situations be candidates for nitrates. Some patients with CAD could experience an ACS within 24-48 hours of taking a PDE5 inhibitor.[3]

In order to study this drug-drug interaction, Parker and colleagues[4] performed a randomized, double-blind, crossover trial to evaluate the effect of IV NTG in 34 men with stable CAD who received sildenafil 100 mg or placebo. Telemetry monitoring was used to assess supine blood pressure and heart rate at baseline and every 3 minutes during the assessment periods, which were 15 minutes prior to sildenafil/placebo administration, 15 minutes prior to NTG initiation, and 9 minutes after each change in NTG dose level (maximum 160 µg/min).

Sildenafil administration resulted in a mean ± standard deviation maximum decrease in systolic/diastolic blood pressure of 12 ± 12/8 ± 8 mm Hg compared with 5 ± 11/4 ± 7 mm Hg after placebo administration. Heart rate change after sildenafil was 2 ± 3 beats per minute and -1 ± 4 beats per minute for placebo. The NTG dose (median maximum) was 80 µg/min (range 0-160) for the sildenafil phase and 160 µg/min (range 20-160) for the placebo phase. The maximum rate of 160 µg/min was tolerated by 8 (25%) men during the sildenafil phase vs 19 (59%) during the placebo phase (P = .0008). Hypotension occurred in significantly more patients in the sildenafil group. The authors recommend caution when extrapolating these results to other subgroups of patients, including those with ACS.

As treatment of ACS should include all of the recommended therapeutic interventions, nitrates may not be required for a patient who develops an ACS 24-48 hours after administration of a PDE5 inhibitor.[3] Some suggest that recent sildenafil administration may not be absolutely contraindicated in patients who require IV NTG as long as the blood pressure is monitored appropriately.[3]

The American College of Cardiology (ACC) and American Heart Association (AHA) joint guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction recommend that NTG or nitrates not be given to these patients within 24 hours of sildenafil.[5] Nitrates should also be avoided after use of other PDE5 inhibitors.[5,6] An ACC/AHA expert consensus document suggests that nitrates may be considered 24 hours after sildenafil dosing. Further delay may be necessary in the patient who might have a prolonged elimination half-life of sildenafil due to renal or hepatic dysfunction or coadministration of a cytochrome P450 3A4 inhibitor. If NTG is initiated in such circumstances, caution and careful monitoring are necessary.[7]

In conclusion, administration of any form of nitrates in a patient who has taken sildenafil poses a real and serious risk for serious hypotension. Coadministration is contraindicated and should be avoided.

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