Sildenafil Citrate

7 DRUG INTERACTIONS • Sildenafil can potentiate the hypotensive effects of nitrates, alpha blockers, and anti-hypertensives ( 4.1 , 5.5 , 7.1 , 7.2 , 7.3 , 12.2 ) • With concomitant use of alpha blockers, initiate sildenafil at 25 mg dose ( 2.3 ) • CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin): Increase sildenafil exposure ( 2.4 , 7.4 , 12.3 ) o Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48 hour period ( 2.4 , 5.6 ) o Erythromycin or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, saquinavir): Consider a starting dose of 25 mg ( 2.4 , 7.4 ) 7.1 Nitrates Administration of sildenafil with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in a 160% and 182% increases in sildenafil C max and AUC, respectively. A starting dose of 25 mg of sildenafil should be considered in patients taking erythromycin or strong CYP3A4 inhibitors (such as saquinavir, ketoconazole, itraconazole) [ see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ].

7 DRUG INTERACTIONS • Sildenafil can potentiate the hypotensive effects of nitrates, alpha blockers, and anti-hypertensives ( 4.1 , 5.5 , 7.1 , 7.2 , 7.3 , 12.2 ) • With concomitant use of alpha blockers, initiate sildenafil at 25 mg dose ( 2.3 ) • CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin): Increase sildenafil exposure ( 2.4 , 7.4 , 12.3 ) o Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48 hour period ( 2.4 , 5.6 ) o Erythromycin or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, saquinavir): Consider a starting dose of 25 mg ( 2.4 , 7.4 ) 7.1 Nitrates Administration of sildenafil with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole could be expected to have greater effects than seen with saquinavir. A starting dose of 25 mg of sildenafil should be considered in patients taking erythromycin or strong CYP3A4 inhibitors (such as saquinavir, ketoconazole, itraconazole) [ see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ].

7 DRUG INTERACTIONS • Sildenafil can potentiate the hypotensive effects of nitrates, alpha blockers, and anti-hypertensives ( 4.1 , 5.5 , 7.1 , 7.2 , 7.3 , 12.2 ) • With concomitant use of alpha blockers, initiate sildenafil at 25 mg dose ( 2.3 ) • CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin): Increase sildenafil exposure ( 2.4 , 7.4 , 12.3 ) o Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48 hour period ( 2.4 , 5.6 ) o Erythromycin or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, saquinavir): Consider a starting dose of 25 mg ( 2.4 , 7.4 ) 7.1 Nitrates Administration of sildenafil with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole could be expected to have greater effects than seen with saquinavir. A starting dose of 25 mg of sildenafil should be considered in patients taking erythromycin or strong CYP3A4 inhibitors (such as saquinavir, ketoconazole, itraconazole) [ see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ].

Avoid use with VIAGRA or other PDE-5 inhibitors.

Administration of sildenafil with nitrates is contraindicated. Sildenafil potentiates the hypotensive effects of nitrates through effects on the nitric oxide/cGMP pathway.

Concomitant use is contraindicated; PDE-5 inhibitors potentiate hypotensive effects of organic nitrates.

7 DRUG INTERACTIONS • Sildenafil can potentiate the hypotensive effects of nitrates, alpha blockers, and anti-hypertensives ( 4.1 , 5.5 , 7.1 , 7.2 , 7.3 , 12.2 ) • With concomitant use of alpha blockers, initiate sildenafil at 25 mg dose ( 2.3 ) • CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin): Increase sildenafil exposure ( 2.4 , 7.4 , 12.3 ) o Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48 hour period ( 2.4 , 5.6 ) o Erythromycin or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, saquinavir): Consider a starting dose of 25 mg ( 2.4 , 7.4 ) 7.1 Nitrates Administration of sildenafil with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. 7.4 Ritonavir and other CYP3A4 inhibitors Co-administration of ritonavir, a strong CYP3A4 inhibitor, greatly increased the systemic exposure of sildenafil (11-fold increase in AUC).

7 DRUG INTERACTIONS • Sildenafil can potentiate the hypotensive effects of nitrates, alpha blockers, and anti-hypertensives ( 4.1 , 5.5 , 7.1 , 7.2 , 7.3 , 12.2 ) • With concomitant use of alpha blockers, initiate sildenafil at 25 mg dose ( 2.3 ) • CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin): Increase sildenafil exposure ( 2.4 , 7.4 , 12.3 ) o Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48 hour period ( 2.4 , 5.6 ) o Erythromycin or strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, saquinavir): Consider a starting dose of 25 mg ( 2.4 , 7.4 ) 7.1 Nitrates Administration of sildenafil with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Co-administration of saquinavir, a strong CYP3A4 inhibitor, resulted in 140% and 210% increases in sildenafil C max and AUC, respectively. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole could be expected to have greater effects than seen with saquinavir.

Concomitant use with other PDE-5 inhibitors including Viagra should be avoided.

Alpha-blockers have potential additive blood pressure lowering effects with sildenafil. Initiate sildenafil at lowest dose in patients already stable on alpha blocker therapy.

Potential additive blood pressure-lowering effects. Initiate sildenafil at lowest dose after patients are stable on alpha-blocker therapy.

Co-administration with amlodipine results in additional reduction in blood pressure (mean 8 mmHg systolic and 7 mmHg diastolic).

Bosentan decreases sildenafil exposure; dose up-titration of sildenafil may be needed when initiating treatment.

Alpha-blocker causing additive blood pressure lowering effects; mean additional reductions of 7/7 to 11/4 mmHg observed with reports of symptomatic postural hypotension.

Sildenafil 50 mg given with alcohol did not potentiate the hypotensive effect of alcohol in health subjects at mean maximum blood alcohol levels of 0.08%.