A 58 y/o male presents with complaints of erectile dysfunction (ED). He’s otherwise healthy with some benign prostatic hyperplasia (BPH) for which he uses doxazosin [Cardura®]. He saw a commercial on TV with Mike Ditka for vardenafil [Levitra®], a phosphodiesterase inhibitor similar to Viagra® and Cialis® and was wondering if this could help his situation. He has no other health issues and is not on any organic nitrates, to include as needed SL nitroglycerin. His labs are WNL and he has no other significant medical history. You write him a prescription for Levitra® according to the guidelines at your facility.  About 2 hours later, you get a message from the pharmacy telling you there’s a problem with this patient’s prescription.

You’re certain the patient is not on nitrates and doesn’t have cardiovascular disease and is not on flying status and his plan doesn’t require a prior authorization, so
what’s the problem?
 

SELECT  here for discussion

Labeling for these agents (phosphodiesterase inhibitors, type 5) has been changed to include a drug-drug interaction with alpha 1 adrenergic inhibitors to include prazosin (Minipres®], doxazosin [Cardura®], and terazosin [Hytrin®]. When given together (within 4 hours) the antihypertensive effect of the alpha-blocker is potentiated and has resulted in fainting. See below for more details.

From MICROmedex:

Vardenafil [Levitra®]

1.    Summary: Significant hypotension developed in a substantial number of subjects when vardenafil 10 or 20 mg was given to healthy volunteers either simultaneously or 6 hours after a single dose of terazosin 10 mg. When vardenafil 10 mg and terazosin 10 mg were simultaneously administered, 6 of 8 subjects experienced a standing systolic blood pressure of less than 85 mm Hg. When vardenafil 20 mg and terazosin 10 mg were simultaneously administered, 2 of 9 subjects experienced a standing systolic blood pressure of less than 85 mm Hg.

Seven of 28 subjects who received vardenafil 20 mg experienced a decrease in standing systolic blood pressure below 85 mm Hg when vardenafil dosing was separated from terazosin 10 mg by 6 hours. In a similar study involving tamsulosin, 1 of 24 subjects receiving vardenafil 20 mg and tamsulosin 0.4 mg separated by 6 hours experienced a standing systolic blood pressure below 85 mm Hg. The administration of lower doses of vardenafil with alpha-blockers has not been completely evaluated to determine if they can be safely administered together.

Based on these data, vardenafil should not be used in patients on alpha-1 adrenergic blocker therapy (Sweetman, 2004; Prod Info Levitra®, 2003; Prod Info Hytrin®, 2002; Prod Info Minipress®, 2000; Prod Info Dibenzyline®, 2000; Prod Info Phentolamine mesylate, 1999; Jardin et al, 1993; Yoshioka et al, 1990; van Zwieten et al, 1990; Rosenthal, 1987; Taylor et al, 1983). 

2.    Adverse Effect: potentiation of hypotensive effects

3.    Clinical Management: Because the coadministration of alpha-1 adrenergic blockers and vardenafil can produce hypotension, vardenafil is contraindicated in patients taking alpha-1 adrenergic blockers.

4.    Severity: major

5.    Onset: rapid

6.    Documentation: fair

7.    Probable Mechanism: unknown Tadalafil [Cialis®]

1.    Summary: Administration of tadalafil to patients taking alpha-adrenergic antagonists other than tamsulosin 0.4 mg once daily is contraindicated. In a drug-drug interaction study, healthy subjects taking tadalafil 20 mg in addition to doxazosin 8 mg daily, significant augmentation of the blood-pressure-lowering effect of doxazosin occurred. No significant decreases in blood pressure were observed when tadalafil 20 mg was administered to healthy subjects taking tamsulosin 0.4 mg once daily (Prod Info Cialis®, 2003).

2.    Adverse Effect: potentiation of hypotensive effects

3.    Clinical Management: Because the coadministration of alpha-1adrenergic blockers and tadalafil can produce hypotension, tadalafil is contraindicated in patients taking alpha-1 adrenergic blockers.

4.    Severity: major

5.    Onset: rapid

6.    Documentation: fair

7.    Probable Mechanism: unknown

Sildenafil [Viagra®]

From the FDA-approved product package insert – Precautions - “When the alpha blocker doxazosin (4 mg) and VIAGRA (25 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH), mean additional reductions of supine blood pressure of 7 mmHg systolic and 7 mmHg diastolic were observed. When higher doses of VIAGRA and doxazosin (4 mg) were administered simultaneously, there were infrequent reports of patients who experienced symptomatic postural hypotension within 1 to 4 hours of dosing. Simultaneous administration of VIAGRA to patients taking alpha-blocker therapy may lead to symptomatic hypotension in some patients. Therefore, VIAGRA doses above 25 mg should not be taken within 4 hours of taking an alpha-blocker.”

Package labeling includes a precaution stating ingestion of sildenafil within 4 hours of an alpha-blocker could cause fainting.  FYI – Sildenafil is NOT waiverable in pilots because it can (rarely) cause visual problems in patients. This can include a blue haze with transient increased brightness, pulsating blue light, and color vision disturbances.