Medication Interactions

Introduction to PDE5 Inhibitors and Nitrates

PDE5 inhibitors, such as sildenafil, should not be used with nitrates due to the risk of potentially fatal hypotension, as recommended by the American Heart Association, American College of Cardiology, and American Urological Association 1, 2, 3, 4, 5, 6
The combination of PDE5 inhibitors with nitrates is absolutely contraindicated due to the risk of severe hypotension that can be fatal, with a strength of evidence that is clear and consistent, as supported by the American College of Cardiology, European Heart Journal, and other guideline societies 1, 2, 3, 4, 5, 6

The initial recommended dose of sildenafil is 50 mg taken approximately 1 hour before sexual activity, according to the American Urological Association 2
Lower starting doses of sildenafil (25mg) are recommended when used with certain medications such as ritonavir, ketoconazole, itraconazole, erythromycin, clarithromycin, and cimetidine, due to potential drug interactions, as recommended by the American Urological Association 2

The following medications have specific recommendations for use with PDE5 inhibitors:

Medication	Recommendation
Ritonavir	lower starting dose of sildenafil (25mg)
Ketoconazole	lower starting dose of sildenafil (25mg)
Itraconazole	lower starting dose of sildenafil (25mg)
Erythromycin	lower starting dose of sildenafil (25mg)
Clarithromycin	lower starting dose of sildenafil (25mg)
Cimetidine	lower starting dose of sildenafil (25mg)
Famotidine	no dose adjustment necessary

For patients with creatinine clearance 30-50 mL/min, the recommended starting doses are:
PDE-5 Inhibitor Starting Dose
Sildenafil 25mg
Tadalafil 5mg once daily, maximum 10mg every 48 hours
For patients with creatinine clearance <30 mL/min, the recommended limitations are:
PDE-5 Inhibitor Limitation
Sildenafil 25mg every 48 hours
Tadalafil not recommended for once-daily use; for as-needed use, limit to 5mg every 72 hours

PDE-5 Inhibitor	Starting Dose
Sildenafil	25mg
Tadalafil	5mg once daily, maximum 10mg every 48 hours

PDE-5 Inhibitor	Limitation
Sildenafil	25mg every 48 hours
Tadalafil	not recommended for once-daily use; for as-needed use, limit to 5mg every 72 hours

For patients with mild to moderate hepatic impairment, the recommended starting doses are:
PDE-5 Inhibitor Starting Dose
Sildenafil and vardenafil 25mg and 5mg respectively
Tadalafil maximum dose should not exceed 10mg

PDE-5 Inhibitor	Starting Dose
Sildenafil and vardenafil	25mg and 5mg respectively
Tadalafil	maximum dose should not exceed 10mg

Patients must remove nitroglycerin patches at least 24 hours before using sildenafil due to the risk of potentially fatal hypotension, as recommended by the American Heart Association 10
Nitrates should not be used within 24 hours of sildenafil use, according to the American College of Cardiology 10
The administration of nitrates to a patient who has taken sildenafil could lead to severe and potentially fatal hypotension, compromised coronary perfusion, and severe cardiovascular complications, as recommended by the American Heart Association and American College of Cardiology 1, 3, 5
Patients on PDE5 inhibitors should be educated about potential drug interactions and advised to report any symptoms of hypotension, as recommended by the American College of Cardiology 5

In a cardiac emergency requiring nitrates, patients should inform medical personnel about recent PDE5 inhibitor use, as recommended by the American Heart Association 2, 3
Patients with coronary artery disease taking nitrates who wish to use PDE5 inhibitors should consider consulting with a cardiologist to assess whether nitrate therapy can be safely discontinued, as suggested by the American Heart Association 8