REVATIO

Absorption and Distribution REVATIO is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25 to 63%). Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. When REVATIO is taken with a high-fat meal, the rate of absorption is reduced, with a mean delay in T max of 60 minutes and a mean reduction in C max of 29%. The mean steady state volume of distribution (Vss) for sildenafil is 1...

SUPER-1 (NCT00644605) - REVATIO Monotherapy [20 mg, 40 mg, and 80 mg Three Times a Day] A randomized, double-blind, placebo-controlled study of REVATIO (SUPER-1) was conducted in 277 patients with PAH (defined as a mean pulmonary artery pressure ≥ 25 mmHg at rest with a pulmonary capillary wedge pressure < 15 mmHg). Patients were predominantly WHO Functional Classes II-III. Allowed background therapy included a combination of anticoagulants, digoxin, calcium channel blockers, diuretics, and oxygen. The use of prostacyclin analogues, endothelin receptor antagonists, and arginine supplementation...

The following serious adverse events are discussed elsewhere in the labeling:

• Hypotension [see Warnings and Precautions (5.1) ]
• Vision Loss [see Warnings and Precautions (5.4) ]
• Hearing Loss [see Warnings and Precautions (5.5) ]
• Priapism [see Warnings and Precautions (5.7) ]
• Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell Disease [see Warnings and Precautions (5.8) ] Adults: Headache, dyspepsia, flushing, pain in limb, myalgia, back pain and diarr...

REVATIO is contraindicated in patients with:

• Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.1) ] .
• Concomitant use of riociguat, a guanylate cyclase stimulator. Phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.
• Know...

• Vasodilation effects may be more common in patients with hypotension or on antihypertensive therapy. ( 5.1 )
• Use in pulmonary veno-occlusive disease (PVOD) may cause pulmonary edema and is not recommended. ( 5.2 )
• Hearing or visual impairment: Seek medical attention if sudden decrease or loss of vision or hearing occurs. ( 5.4 , 5.5 )
• Pulmonary hypertension (PH) secondary to sickle cell disease: REVATIO may cause serious vaso-occlusive crises. ( 5.8 ) 5.1 Hypotension REVATIO has vasodila...

7 DRUG INTERACTIONS Nitrates Concomitant use of REVATIO with nitrates in any form is contraindicated [see Contraindications (4) ] . Strong CYP3A Inhibitors Concomitant use of REVATIO with strong CYP3A inhibitors is not recommended [see Clinical Pharmacology (12.3) ] . Moderate-to-Strong CYP3A Inducers Concomitant use of REVATIO with moderate-to-strong CYP3A inducers (such as bosentan) decreases th...