Vardenafil

In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] .

In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] .

In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] . Moderate CYP3A4 inhibitors Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in vardenafil C max when co-administered with vardenafil 5 mg in healthy volunteers [see Dosage and Administration ( 2 ) and Warnings and Precautions ( 5 )].

PDE5 inhibitor potentiates hypotensive effects of isosorbide dinitrate. Contraindicated.

In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] . [See Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5 ).] Indinavir (800 mg t.i.d.) co-administered with vardenafil 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. Ritonavir and Indinavir: Upon concomitant administration of 5 mg vardenafil with 600 mg b.i.d.

In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] .

In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] . Strong CYP3A4 inhibitors Ketoconazole (200 mg once daily) produced a 10-fold increase in vardenafil area under the curve (AUC) and a 4-fold increase in maximum concentration (C max ) when co-administered with vardenafil 5 mg in healthy volunteers.

Do not use moderate or strong CYP3A4 inhibitors with vardenafil as coadministration results in significant increases in plasma vardenafil concentrations.

Concomitant use is contraindicated. Vardenafil potentiates blood pressure lowering effects and increases heart rate when taken within 8 hours of nitrates.

Concomitant use of vardenafil and nitric oxide donors is contraindicated.

PDE-5 inhibitor that potentiates hypotensive effects of nitroglycerin. Contraindicated with nitroglycerin.

PDE5 inhibitor that potentiates hypotensive effects of nitroglycerin. Concomitant use is contraindicated.

PDE-5 inhibitor that potentiates hypotensive effects of nitroglycerin. Concomitant use is contraindicated.

Co-administration with vardenafil is contraindicated because of hypotension.

In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] . [See Dosage and Administration (2.4) and Warnings and Precautions ( 5 ).] Ritonavir (600 mg b.i.d.) co-administered with vardenafil 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.

In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] .

Alpha-blocker interaction with additive blood pressure lowering effects. Clinical pharmacology studies conducted; caution advised when co-administered.

Concomitant use may cause additive blood pressure lowering effects. Patients should not initiate vardenafil with alpha-blockers; caution advised if co-administered.

Alpha-blocker interaction with additive blood pressure lowering effects. Clinical pharmacology studies conducted; caution advised when co-administered.

Alpha-blocker interaction with additive blood pressure lowering effects. Clinical pharmacology studies conducted; caution advised when co-administered.

Vardenafil may add to blood pressure lowering effects of antihypertensive medications.

Deferasirox may induce CYP3A4 resulting in decreased vardenafil concentration. Monitor for reduced effectiveness.

Both sapropterin and PDE-5 inhibitors may induce vasorelaxation, potentially reducing blood pressure.

PDE-5 inhibitor that with sepiapterin may cause additive vasorelaxation and blood pressure reduction. Monitor blood pressure.

In vivo studies Nifedipine: Vardenafil 20 mg (film-coated tablets), when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the relative AUC or C max of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil when taken in combination. Vardenafil orally disintegrating tablet, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily in patients whose hypertension was controlled with nifedipine, produced mean additional supine systolic/diastolic blood pressure reductions of 3/4 mmHg (age group 65 to 69 years) and 5/5 mmHg (age group 70 to 80 years) compared to placebo.