REVATIO is indicated for the treatment of pulmonary arterial hypertension (WHO Group
I) to improve exercise ability. The efficacy of REVATIO has not been evaluated in
patients currently on bosentan therapy.
The use of REVATIO and organic nitrates in any form, at any time, is contraindicated.
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 CYP3A4 inducers, including bosentan;
and more potent inducers such as barbiturates, carbamazepine, phenytoin, efavirenz,
nevirapine, rifampin, and rifabutin, may alter plasma levels of either or both medications.
Dosage adjustment may be necessary.
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.
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.
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.
Caution is advised when PDE5 inhibitors, such as REVATIO, are administered with
α−blockers as both are vasodilators with blood pressure lowering effects.
Patients with the following characteristics did not participate in the preapproval
clinical trial: patients who have suffered a myocardial infarction, stroke, or life-threatening
arrhythmia within the last 6 months, unstable angina, hypertension (BP>170/110),
retinitis pigmentosa, or patients on bosentan. 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 should be used with caution in patients with anatomical deformation of the
penis or patients who have conditions which may predispose them to priapism.
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%).
Non-arteritic anterior ischemic optic neuropathy (NAION) has been reported rarely
post-marketing in temporal association with the use of PDE5 inhibitors for the treatment
of erectile dysfunction, including sildenafil. It is not possible to determine if
these events are related to PDE5 inhibitors or to other factors. Physicians should
advise patients to seek immediate medical attention in the event of sudden loss
of vision while taking PDE5 inhibitors, including REVATIO.
Sudden decrease or loss of hearing has been rarely 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.