Sildenafil

Brand names: Revatio, Viagra, sildenafil citrate, Sildenafil, Sildenafil Citrate, sildenafil, SILDENAFIL CITRATE, SILDENAFIL

Warnings

Critical Contraindications: "Administration of VIAGRA to patients using nitric oxide donors, such as organic nitrates or organic nitrites in any form" is contraindicated due to severe hypotensive effects. Cannot be used with guanylate cyclase stimulators like riociguat. Contraindicated in patients with known hypersensitivity to sildenafil. Major Warnings: Vision Loss - "Stop use of all PDE5 inhibitors...and seek medical attention in the event of a sudden loss of vision" (risk of NAION). Priapism - erection persisting longer than 4 hours requires immediate medical attention. Hearing Loss - sudden decrease or loss of hearing reported post-marketing. Cardiovascular Risk - sexual activity may pose cardiac risk in patients with preexisting cardiovascular disease.

Contraindications

4 CONTRAINDICATIONS Administration of sildenafil tablets to patients using nitric oxide donors, such as organic nitrates or organic nitrites in any form. Sildenafil citrate was shown to potentiate the hypotensive effect of nitrates ( 4.1 , 7.1 , 12.2 ) Known hypersensitivity to sildenafil or any component of tablet ( 4.2 ) Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 4.3 ) 4.1 Nitrates Consistent with its known effects on the nitric oxide/cGMP pathway [ see Clinical Pharmacology ( 12.1 , 12.2 ) ], sildenafil citrate was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using nitric oxide donors such as organic nitrates or organic nitrites in any form either regularly and/or intermittently is therefore contraindicated. After patients have taken sildenafil tablets, it is unknown when nitrates, if necessary, can be safely administered. Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely co-administered at this time point [ see Dosage and Administration ( 2.3 ), Drug Interactions ( 7.1 ), and Clinical Pharmacology ( 12.2 ) ]. 4.2 Hypersensitivity Reactions Sildenafil citrate is contraindicated in patients with a known hypersensitivity to sildenafil, as contained in sildenafil tablets and REVATIO, or any component of the tablet. Hypersensitivity reactions have been reported, including rash and urticaria [ see Adverse Reactions ( 6.1 ) ] . 4.3 Concomitant Guanylate Cyclase (GC) Stimulators Do not use sildenafil tablets in patients who are using a GC stimulator, such as riociguat. PDE5 inhibitors, including sildenafil citrate, may potentiate the hypotensive effects of GC stimulators.

Overdose

10 OVERDOSAGE In studies with healthy volunteers of single doses up to 800 mg, adverse reactions were similar to those seen at lower doses but incidence rates and severities were increased. In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is not eliminated in the urine.

Drug interactions

7 DRUG INTERACTIONS Sildenafil citrate 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 citrate at 25 mg dose ( 2.3 ) CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin): Increase sildenafil citrate exposure ( 2.4 , 7.4 , 12.3 ) Ritonavir: Do not exceed a maximum single dose of 25 mg in a 48 hour period ( 2.4 , 5.6 ) 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 tablets with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil citrate was shown to potentiate the hypotensive effects of nitrates [ see Dosage and Administration ( 2.3 ), Contraindications ( 4.1 ), Clinical Pharmacology ( 12.2 ) ] . 7.2 Alpha-blockers Use caution when co-administering alpha-blockers with sildenafil tablets because of potential additive blood pressure-lowering effects. When sildenafil tablets are co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating sildenafil tablets treatment and sildenafil tablets should be initiated at the lowest dose [ see Dosage and Administration ( 2.3 ),Warnings and Precautions ( 5.5 ), Clinical Pharmacology ( 12.2 ) ] . 7.3 Amlodipine When sildenafil tablets 100 mg were co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic [ see Warnings and Precautions ( 5.5 ), Clinical Pharmacology ( 12.2 ) ]. 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). It is therefore recommended not to exceed a maximum single dose of 25 mg of sildenafil citrate in a 48 hour period [ see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.6 ), Clinical Pharmacology ( 12.3 ) ]. Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in a 160% and 182% increases in sildenafil C max and AUC, respectively. 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. A starting dose of 25 mg of sildenafil tablets 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 ) ] . 7.5 Alcohol In a drug-drug interaction study sildenafil 50 mg given with alcohol 0.5 g/kg in which mean maximum blood alcohol levels of 0.08% was achieved, sildenafil did not potentiate the hypotensive effect of alcohol in healthy volunteers [ see Clinical Pharmacology ( 12.2 ) ].

Uses

"VIAGRA is indicated for the treatment of erectile dysfunction." A phosphodiesterase-5 (PDE5) inhibitor used to help men achieve and maintain erections during sexual activity.

Dosage forms & strengths

Tablet Tablet, Film Coated TABLET, FILM COATED FOR SUSPENSION TABLET POWDER POWDER, FOR SUSPENSION

SILDENAFIL CITRATE 100 mg SILDENAFIL CITRATE 20 mg SILDENAFIL CITRATE 25 mg SILDENAFIL CITRATE 50 mg SILDENAFIL CITRATE 50 mg/1 SILDENAFIL CITRATE 100 mg/1 SILDENAFIL CITRATE 25 mg/1 SILDENAFIL CITRATE 20 mg/1 SILDENAFIL CITRATE 10 mg/mL SILDENAFIL CITRATE 1 g/g SILDENAFIL 10 mg/mL

2 DOSAGE AND ADMINISTRATION For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. However, sildenafil tablets may be taken anywhere from 30 minutes to 4 hours before sexual activity ( 2.1 ) Based on effectiveness and toleration, may increase to a maximum of 100 mg or decrease to 25 mg ( 2.1 ) Maximum recommended dosing frequency is once per day ( 2.1 ) 2.1 Dosage Information For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. However, sildenafil tablets may be taken anywhere from 30 minutes to 4 hours before sexual activity. The maximum recommended dosing frequency is once per day. Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg. 2.2 Use with Food Sildenafil tablets may be taken with or without food. 2.3 Dosage Adjustments in Specific Situations Sildenafil citrate was shown to potentiate the hypotensive effects of nitrates and its administration in patients who use nitric oxide donors such as organic nitrates or organic nitrites in any form is therefore contraindicated [ see Contraindications ( 4.1 ), Drug Interactions ( 7.1 ), and Clinical Pharmacology ( 12.2 ) ] . When sildenafil tablets are co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating sildenafil tablets treatment and sildenafil tablets should be initiated at 25 mg [ see Warnings and Precautions ( 5.5 ), Drug Interactions ( 7.2 ), and Clinical Pharmacology ( 12.2 ) ]. 2.4 Dosage Adjustments Due to Drug Interactions Ritonavir The recommended dose for ritonavir-treated patients is 25 mg prior to sexual activity and the recommended maximum dose is 25 mg within a 48 hour period because concomitant administration increased the blood levels of sildenafil by 11-fold [ see Warnings and Precautions ( 5.6 ), Drug Interactions ( 7.4 ), and Clinical Pharmacology ( 12.3 ) ]. CYP3A4 Inhibitors Consider a starting dose of 25 mg in patients treated with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, or saquinavir) or erythromycin. Clinical data have shown that co-administration with saquinavir or erythromycin increased plasma levels of sildenafil by about 3 fold [ see Drug Interactions ( 7.4 ) and Clinical Pharmacology ( 12.3 ) ]. 2.5 Dosage Adjustments in Special Populations Consider a starting dose of 25 mg in patients > 65 years, patients with hepatic impairment (e.g., cirrhosis), and patients with severe renal impairment (creatinine clearance <30 mL/minute) because administration of sildenafil tablets in these patients resulted in higher plasma levels of sildenafil [ see Use in Specific Populations ( 8.5 , 8.6 , 8.7 ) and Clinical Pharmacology ( 12.3 ) ] .

Ingredients

Inactive:

Sildenafil tablets, USP are indicated for the treatment of pulmonary arterial hypertension (WHO Group I) in adults to improve exercise ability and delay clinical worsening. The delay in clinical worsening was demonstrated when sildenafil tablets was added to background epoprostenol therapy [see Clinical Studies (14)]. Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%). Limitation of Use: Adding sildenafil to bosentan therapy does not result in any beneficial effect on exercise capacity [see Clinical Studies (14)].