Vardenafil Hydrochloride

Concomitant use of vardenafil hydrochloride and nitrates is contraindicated. Vardenafil potentiates the blood pressure lowering effects of nitrates.

Concomitant use of vardenafil hydrochloride and nitric oxide donors is contraindicated.

Concomitant use of vardenafil hydrochloride and nitroglycerin is contraindicated. Vardenafil potentiates the blood pressure lowering effects.

Strong CYP3A4 inhibitor producing a 10-fold increase in vardenafil AUC and 4-fold increase in Cmax, significantly increasing vardenafil exposure and risk of adverse effects.

Vardenafil hydrochloride may add to the blood pressure lowering effects of antihypertensive agents.

Caution is advised when vardenafil is co-administered with alfuzosin. Both are vasodilators with blood-pressure-lowering effects; additive effect on blood pressure may be anticipated.

Moderate CYP3A4 inhibitors Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in C max when co­ administered with vardenafil hydrochloride tablets 5 mg in healthy volunteers. It is recommended not to exceed a single 5 mg dose of vardenafil hydrochloride tablets in a 24-hour period when used in combination with erythromycin.

Caution is advised when vardenafil is co-administered with tamsulosin. Both are vasodilators with blood-pressure-lowering effects; additive effect on blood pressure may be anticipated.

Caution is advised when vardenafil is co-administered with terazosin. Both are vasodilators with blood-pressure-lowering effects; additive effect on blood pressure may be anticipated.

Vardenafil did not potentiate the hypotensive effects of alcohol during the 4-hour observation period in healthy volunteers.

[See Dosage and Administration (2.4) and Warnings and Precautions (5) .] Indinavir (800 mg t.i.d.) co-administered with vardenafil hydrochloride tablets 10 mg resulted in a 16-fold increase in vardenafil AUC, a 7-fold increase in vardenafil C max and a 2-fold increase in vardenafil half-life. It is recommended not to exceed a single 2.5 mg vardenafil hydrochloride tablets dose in a 24-hour period when used in combination with indinavir. Ritonavir and Indinavir: Upon concomitant administration of 5 mg of vardenafil hydrochloride tablets with 600 mg BID ritonavir, the C max and AUC of ritonavir were reduced by approximately 20%.

In vivo studies Nifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the AUC or C max of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil hydrochloride tablets when taken in combination. In these patients whose hypertension was controlled with nifedipine, vardenafil hydrochloride tablets 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo.

[See Dosage and Administration (2.4) and Warnings and Precautions (5.2) .] Ritonavir (600 mg b.i.d.) co-administered with vardenafil hydrochloride tablets 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13­ fold increase in vardenafil C max . The interaction is a consequence of blocking hepatic metabolism of vardenafil by ritonavir, a HIV protease inhibitor and a highly strong CYP3A4 inhibitor, which also inhibits CYP2C9. Ritonavir significantly prolonged the half-life of vardenafil to 26 hours.