Absolute Contraindications for PDE-5 Inhibitors
PDE-5 inhibitors are absolutely contraindicated in patients taking any form of organic nitrates (regularly or intermittently) due to life-threatening synergistic hypotension. 1, 2
Primary Contraindications
Nitrate Use (Absolute)
- Any concurrent nitrate therapy including nitroglycerin, isosorbide dinitrate, or any organic nitrate formulation is an absolute contraindication 1, 2
- This applies to both regular and intermittent nitrate use 1
- If a patient has taken a PDE-5 inhibitor, at least 12 hours must elapse after the last dose before nitrate administration can be considered in life-threatening situations 2
- For short-acting PDE-5 inhibitors (sildenafil, vardenafil), nitrates may generally be taken 24 hours after the last dose; for long-acting agents (tadalafil), wait 48 hours 3
Guanylate Cyclase Stimulators (Absolute)
- Concomitant use with GC stimulators (riociguat, vericiguat) is contraindicated due to potentiation of hypotensive effects 2
Hypersensitivity (Absolute)
- Known hypersensitivity to any component of the PDE-5 inhibitor formulation 2
Strong CYP3A4 Inhibitors (Absolute for Avanafil)
- Do not use avanafil with strong CYP3A4 inhibitors including ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, and telithromycin 2
High-Risk Patient Groups (Not Recommended)
Recent Cardiovascular Events
PDE-5 inhibitors are not recommended for patients who have experienced within the last 6 months: 2
- Myocardial infarction
- Stroke
- Life-threatening arrhythmia
- Coronary revascularization
Severe Hemodynamic Instability
Do not use in patients with: 2
- Resting hypotension (BP <90/50 mmHg)
- Severe hypertension (BP >170/100 mmHg)
- Unstable angina
- Angina occurring with sexual intercourse
- New York Heart Association Class 2 or greater congestive heart failure
Left Ventricular Outflow Obstruction
Patients with aortic stenosis or idiopathic hypertrophic subaortic stenosis are particularly sensitive to vasodilatory effects and should not receive PDE-5 inhibitors 2
Severely Impaired Autonomic Control
Patients with severely impaired autonomic control of blood pressure are at high risk for adverse hemodynamic effects 2
Special Caution Required (Use With Extreme Care)
Alpha-Blocker Combination
- Caution required when combining PDE-5 inhibitors with alpha-blockers (except tamsulosin) due to risk of orthostatic hypotension 4, 5
- Use lowest doses of both agents when combination is necessary 5
- The interaction may be less clinically relevant in patients on long-term alpha-blocker therapy 4
Anatomical Penile Deformities
Use with caution in patients with: 2, 6
- Angulation
- Cavernosal fibrosis
- Peyronie's disease
Conditions Predisposing to Priapism
Exercise caution in patients with: 2, 6
- Sickle cell anemia
- Multiple myeloma
- Leukemia
Pulmonary Hypertension Secondary to Sickle Cell Disease
- PDE-5 inhibitors are not recommended for PAH secondary to sickle cell anemia due to increased risk of vaso-occlusive crises 6
Retinitis Pigmentosa
- Prescribe with caution in patients with retinitis pigmentosa, particularly those with genetic disorders of retinal phosphodiesterases 6
Clinical Pitfalls to Avoid
- Never assume intermittent nitrate use is safe – even occasional nitrate use is an absolute contraindication 1, 2
- Do not combine PDE-5 inhibitors with topical nitrates – the contraindication applies to all nitrate formulations including glyceryl trinitrate 1
- Screen for cardiovascular risk before prescribing – patients unable to walk 1 mile in 20 minutes or climb 2 flights of stairs in 20 seconds without symptoms should be referred to cardiology before ED treatment 1
- Verify medication lists carefully – patients may not recognize alpha-blockers prescribed for benign prostatic hypertrophy as relevant 4