Revatio

Important Safety Information and Indication

Important Safety Information

REVATIO^® (sildenafil) is contraindicated in patients with concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension.

REVATIO is contraindicated in patients with concomitant use of riociguat, a soluble guanylate cyclase (sGC) stimulator medication. PDE5 inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.

REVATIO is contraindicated in patients with a known hypersensitivity to sildenafil or any other ingredient in REVATIO. Hypersensitivity, including anaphylactic reaction, anaphylactic shock, and anaphylactoid reaction has been reported in association with the use of sildenafil.

Use of REVATIO, particularly chronic use, is not recommended in children.

Before starting REVATIO, physicians should carefully consider whether their patients with underlying conditions could be adversely affected by the mild and transient vasodilatory effects of REVATIO on blood pressure. Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD) and administration of REVATIO to these patients is not recommended. Should signs of pulmonary edema occur when sildenafil is administered, the possibility of associated PVOD should be considered.

Caution is advised when PDE5 inhibitors, such as REVATIO, are administered with α−blockers as both are vasodilators with blood pressure lowering effects.

In PAH patients, the concomitant use of vitamin K antagonists and REVATIO resulted in a greater incidence of reports of bleeding (primarily epistaxis) versus placebo. The incidence of epistaxis was higher in patients with PAH secondary to CTD (sildenafil 13%, placebo 0%) than in PPH patients (sildenafil 3%, placebo 2%).

Co-administration of REVATIO with potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, and ritonavir) is not recommended as serum concentrations of sildenafil substantially increase. Co-administration of REVATIO with potent CYP3A4 inducers such as barbiturates, carbamazepine, phenytoin, efavirenz, nevirapine, rifampin, and rifabutin, is expected to cause substantial decreases in plasma levels of sildenafil. Treatment with doses higher than 20 mg three times a day is not recommended.

Non-arteritic anterior ischemic optic neuropathy (NAION) has been reported post-marketing in temporal association with the use of PDE5 inhibitors for the treatment of erectile dysfunction, including sildenafil. Physicians should advise patients to seek immediate medical attention in the event of sudden loss of vision while taking PDE5 inhibitors, including REVATIO. Physicians should also discuss the increased risk of NAION with patients who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators, such as PDE-5 inhibitors.

Sudden decrease or loss of hearing has been reported in temporal association with the intake of PDE5 inhibitors, including REVATIO. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors. Physicians should advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking PDE5 inhibitors, including REVATIO.

REVATIO should be used with caution in patients with anatomical deformation of the penis or patients who have conditions which may predispose them to priapism.

The effectiveness of REVATIO in pulmonary hypertension (PH) secondary to sickle cell anemia has not been established. In a small, prematurely terminated study of patients with PH secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported by patients who received REVATIO than by those randomized to placebo.

Patients with retinitis pigmentosa and patients on bosentan did not participate in the preapproval clinical trial. The safety of REVATIO is unknown in patients with bleeding disorders and patients with active peptic ulceration. In these patients, physicians should prescribe REVATIO with caution.

REVATIO contains sildenafil, the same active ingredient found in VIAGRA^®. Combinations of REVATIO with VIAGRA or other PDE5 inhibitors have not been studied. Patients taking REVATIO should not take VIAGRA or other PDE5 inhibitors.

The most common side effects of REVATIO (placebo-subtracted) were epistaxis (8%), headache (7%), dyspepsia (6%), flushing (6%), and insomnia (6%). Adverse events were generally transient and mild to moderate. Adverse events of REVATIO injection were similar to those seen with oral tablets.

The most common side effects of REVATIO (placebo-subtracted) as an adjunct to intravenous epoprostenol were headache (23%), edema (14%), dyspepsia (14%), pain in extremity (11%), diarrhea (7%), nausea (7%), and nasal congestion (7%).

At doses higher than the recommended 20 mg TID, there was a greater incidence of some adverse events including flushing, diarrhea, myalgia, and visual disturbances.

No dose adjustment required for renal impaired.

No dose adjustment required for mild to moderate hepatic impaired. Severe impairment has not been studied.