Vision loss: Vision loss may occur rarely and be a sign of nonarteritic anterior ischemic optic neuropathy (NAION). Risk may be increased with history of vision loss. Other risk factors for NAION include low cup-to-disc ratio ("crowded disc"), coronary artery disease, diabetes, hypertension, hyperlipidemia, smoking, and >50 years of age. May cause dose-related impairment of color discrimination (blue/green). Use caution in patients with retinitis pigmentosa; a minority have genetic disorders of retinal phosphodiesterases (no safety information available).
Hearing loss: Sudden decrease or loss of hearing has been reported; hearing changes may be accompanied by tinnitus and dizziness. A direct relationship between therapy and hearing loss has not been determined.
Hypotension: Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), those on antihypertensive therapy, with resting hypotension (BP<90/50 mmHg), fluid depletion, or autonomic dysfunction. These patients may be more sensitive to hypotensive actions. Patients should be hemodynamically stable prior to initiating therapy at the lowest possible dose.
Priapism and prolonged erection: Prolong erections lasting longer than 4 hours and priapism (painful erections longer than 6 hours in duration) have been reported infrequently. Advise patient to seek immediate medical assistance for erection longer than 4 hours.
Anatomical penis deformation: Use with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease).
Conditions predisposing to priapism: Use with caution in patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple myeloma, leukemia). All patients should be instructed to seek immediate medical attention if erection persists longer than 4 hours.
Bleeding disorders: Use with caution in patients with bleeding disorders; safety and efficacy have not been established.
Cardiovascular disease: Use with caution in patients with uncontrolled hypertension (>170/110 mmHg); life-threatening arrhythmias, stroke or myocardial infarction within the last 6 months; cardiac failure or coronary artery disease causing unstable angina. Safety and efficacy have not been studied in these patients. There is a degree of cardiac risk associated with sexual activity; therefore, physicians should consider the cardiovascular status of their patients prior to initiating any treatment.
Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; safety and efficacy have not been established.
Coadministration with alpha-blockers: Concomitant administration of sildenafil to patients taking alpha-blocker therapy may lead to symptomatic hypotension. In order to minimize the potential for developing postural hypotension, patients should be hemodynamically stable on alpha-blocker therapy prior to initiating sildenafil treatment. Physicians should advise patients what to do in the event of postural hypotensive symptoms.
Use with ritonavir and other potent CYP3A4 inhibitors: The concomitant administration of the protease inhibitor ritonavir (a highly potent CYP3A4 inhibitor) substantially increases serum concentrations of sildenafil; therefore, co-administration of ritonavir or other potent CYP3A4 inhibitors with sildenafil is not recommended.
Concomitant use with other PDE5 inhibitors: The safety and efficacy of sildenafil when co-administered with other PDE5 inhibitor products has not been studied in PAH patients and such concomitant use is not recommended.
Hepatic impairment: In volunteers with hepatic cirrhosis, sildenafil clearance was reduced, resulting in increases in AUC (84%) and Cmax (47%). No dosage adjustment is required for PAH.
Renal impairment: In patients with severe renal impairment (CrCl 30 mL/min or less), sildenafil clearance was reduced, resulting in approximately double the AUC and Cmax. For PAH, no dosage dysfunction is required.
Effects on ability to drive and use machine: The effect of sildenafil on the ability to drive and use machinery has not been studied. As dizziness and altered vision were reported, patients should be aware of how they might be affected by sildenafil, before driving or operating machinery.
Use in Children: Safety and efficacy of sildenafil in pediatric PAH patients have not been established.
Use in Elderly: The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant diseases and drug therapy observed in the elderly should be considered in dosage selection for the treatment of PAH.