vybrique

Important safety information

Patients should not use VYBRIQUE if sexual activity is inadvisable due to cardiovascular status. ( 5.1 ) Patients should seek emergency treatment if an erection lasts >4 hours. Use VYBRIQUE with caution in patients predisposed to priapism. ( 5.2 ) Patients should stop VYBRIQUE and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of non-arteritic anterior ischemic optic neuropathy (NAION). VYBRIQUE should be used with caution, and only when the anticipated benefits outweigh the risks, in patients with a history of NAION. Patients with a “crowded” optic disc may also be at an increased risk of NAION. ( 5.3 ) Patients should stop VYBRIQUE and seek prompt medical attention in the event of sudden decrease or loss of hearing. ( 5.4 ) Caution is advised when VYBRIQUE is co-administered with alpha-blockers or antihypertensives. Concomitant use may lead to hypotension. ( 5.5 ) Decreased blood pressure, syncope, and prolonged erection may occur at higher sildenafil exposures. In patients taking strong CYP inhibitors such as ritonavir, sildenafil exposure is increased. Decrease in VYBRIQUE dosage is recommended. ( 2.2 , 5.6 ). 5.1 Cardiovascular Risk General There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including VYBRIQUE should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. The following groups of patients were not included in clinical safety and efficacy trials for sildenafil, and therefore, until further information is available, VYBRIQUE is not recommended for use in the following groups: Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months Patients with resting hypotension (BP <90/50 mmHg) or hypertension (BP >170/110 mmHg) Patients with cardiac failure or coronary artery disease causing unstable angina. Blood Pressure Decreases Patients with left ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure can be sensitive to the actions of vasodilators, including VYBRIQUE. As with other PDE5 inhibitors, VYBRIQUE has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers. In healthy subjects aged 18 to 45 years, VYBRIQUE 100 mg resulted in mean maximal decreases relative to placebo of 6 mmHg systolic and 3 mmHg diastolic. In healthy subjects aged 65 years and older, VYBRIQUE 100 mg resulted in mean maximal decreases relative to placebo of 14 mmHg systolic and 8 mmHg diastolic [ see Clinical Pharmacology ( 12.2 ) ]. Prior to prescribing VYBRIQUE, carefully consider whether patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity. 5.2 Prolonged Erection and Priapism Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of sildenafil. In the event of an erection that persists longer than 4 hours, instruct the patient to seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result. Use VYBRIQUE with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie’s disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia). 5.3 Effects on the Eye Advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including VYBRIQUE and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision including permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5-11.8 cases per 100,000 in males aged 50 years and older. An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. Neither the rare post-marketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [see Adverse Reactions ( 6.2 ) ] . Consider whether patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, use PDE5 inhibitors, including VYBRIQUE with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with “crowded” optic disc are also considered at greater risk for NAION compared to the general population, however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including VYBRIQUE, for this uncommon condition. Patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, were not included in the sildenafil citrate clinical trials, and use in these patients is not recommended. 5.4 Sudden Hearing Loss Advise patients to stop taking PDE5 inhibitors, including VYBRIQUE and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including sildenafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [ see Adverse Reactions ( 6.1 , 6.2 ) ]. 5.5 Hypotension when Co-administered with Alpha-blockers or Antihypertensives Alpha-blockers Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including sildenafil, and alpha-adrenergic blocking agents are both vasodilators with blood pressure lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may occur. In some patients, concomitant use of these two drug classes can lower blood pressure significantly [ see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.2 ) ] leading to symptomatic hypotension (e.g., dizziness, lightheadedness, fainting). Consider the following: Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor. Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors. In patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest dose [see Dosage and Administration ( 2.2 ) ] . In patients already taking an optimized dose of a PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure when taking a PDE5 inhibitor. Safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other variables, including intravascular volume depletion and other antihypertensive drugs.…