Contraindication to Phosphodiesterase Inhibitors in This Patient
The absolute contraindication to prescribing oral phosphodiesterase-5 (PDE5) inhibitors to this patient is his current use of sublingual nitroglycerin for stable angina. 1, 2
Mechanism of Dangerous Interaction
PDE5 inhibitors block the enzyme that degrades cyclic guanosine monophosphate (cGMP), which is the same pathway through which nitrates cause vasodilation. 1
When combined, nitrates and PDE5 inhibitors produce markedly exaggerated and prolonged vasodilation, leading to profound hypotension, myocardial infarction, and potentially death. 1
This represents a Class III recommendation (harm) in ACC/AHA guidelines, meaning the combination should never be performed. 1, 3
Specific Time-Based Contraindications
The contraindication is bidirectional and time-dependent based on which PDE5 inhibitor is used:
Sildenafil or vardenafil: No nitrates can be administered within 24 hours after taking these medications. 1, 2
Tadalafil: No nitrates can be administered for at least 48 hours after the last dose due to its longer elimination half-life. 1, 3, 4
Conversely, patients currently using nitrates (like this patient) cannot safely take any PDE5 inhibitor. 2, 5
Why Other Medications Are Not Contraindications
Beta-blockers, ACE inhibitors, and insulin are NOT contraindications to PDE5 inhibitors. 5, 6
When PDE5 inhibitors are combined with most antihypertensive agents (beta-blockers, ACE inhibitors, calcium channel blockers, diuretics), there are typically only small additive decreases in blood pressure without significant increases in adverse events. 5, 7
The interaction with amlodipine (a calcium channel blocker) produces additive but not synergistic blood pressure reductions comparable to sildenafil alone, and is considered safe with appropriate monitoring. 7
Clinical Management Approach
This patient requires alternative management for his erectile dysfunction that does not involve PDE5 inhibitors. 2
Consider optimizing his angina management to potentially eliminate or reduce his need for sublingual nitroglycerin, which could eventually allow PDE5 inhibitor use. 1
Alternative erectile dysfunction treatments include intracavernosal prostaglandin E1 injections, intraurethral alprostadil, vacuum erection devices, or penile prosthesis if other options fail. 8
If angina control allows discontinuation of nitrates, the patient must remain nitrate-free for the appropriate washout period (24-48 hours depending on which PDE5 inhibitor is chosen) before starting therapy. 1, 3
Critical Safety Point
The FDA drug label explicitly states: "Administration of nitroglycerin sublingual tablets are contraindicated in patients who are using a phosphodiesterase-5 (PDE-5) inhibitor (e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride) since these compounds have been shown to potentiate the hypotensive effects of organic nitrates." 2
Between March 1998 and November 1998, the FDA reported 130 deaths associated with sildenafil use, with 16 men having taken or been administered nitroglycerin or organic nitrates. 9