Sildenafil Disease Interactions

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

Alcohol consumption may intensify the pressure-lowering effects of mild vasodilators, such as phosphodiesterase 5 (PDE5) inhibitors. Therefore, patients that consume alcohol should be warned to limit alcohol intake while receiving these agents.

Use of phosphodiesterase-5 (PDE5) inhibitors has been associated with sudden decrease or loss of hearing, which may be accompanied by tinnitus or dizziness. Patients with hearing problems should stop taking these agents and seek prompt medical care.

Phosphodiesterase 5 (PDE-5) inhibitors are cleared predominantly by hepatic metabolism. The pharmacokinetic disposition of these agents has not been assessed in patients with severe hepatic impairment. No dosage modification is recommended for patients with mild to moderate hepatic impairment, however, therapy with these agents should not be administered to patients with severe hepatic impairment. In patients with mild hepatic impairment a lower dose of these agents should be used as initial therapy.

The use of phosphodiesterase 5 (PDE-5) inhibitors has been associated with seizures. Therapy with these agents should be administered cautiously in patients with preexisting seizure disorders.

The safety and efficacy of sildenafil for the treatment of pulmonary hypertension secondary to sickle cell disease has not been established; vaso-occlusive crises requiring hospitalization were more commonly reported in this population.

The safety of sildenafil in patients with bleeding disorders or active peptic ulceration is unknown. In clinical studies, the incidence of bleeding (i.e., epistaxis) was increased in patients with pulmonary arterial hypertension secondary to connective tissue disease and in patients on concomitant therapy with an oral vitamin K antagonist. There have been postmarketing reports of bleeding events in patients treated with sildenafil for erectile dysfunction.

Exposure to sildenafil is increased in patients with renal dysfunction. Lower starting doses of sildenafil for the treatment of erectile dysfunction (ED) are recommended in patients with severe renal impairment (CrCl less than 30 mL/min). When sildenafil is used for the treatment of pulmonary arterial hypertension, no dose adjustment is recommended for any degree of renal impairment.

Sildenafil for the treatment of erectile dysfunction (ED) should be used with caution and only if the benefit outweighs the risk in patients with a history of non-arteritic anterior ischemic optic neuropathy (NAION) or with retinitis pigmentosa. Use of sildenafil for the treatment of pulmonary arterial hypertension is not recommended in patients with retinitis pigmentosa. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking sildenafil; patients taking sildenafil for ED should immediately stop treatment. Most patients who developed NAION during therapy with sildenafil had underlying anatomic or vascular risk factors, including low cup to disc ratio ("crowded disc").