Hypotension when Co-administered with Alpha-blockers or Anti-hypertensives
Physicians should advise patients to stop taking PDE5 inhibitors, including Viagra, 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 Viagra. 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)].\
Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including Viagra, 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).
Consideration should be given to the following:
- Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors. Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor.
- In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest dose [see Dosage and Administration (2.3)].
- In those 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 anti-hypertensive drugs.
Viagra has systemic vasodilatory properties and may further lower blood pressure in patients taking anti-hypertensive medications.
In a separate drug interaction study, when amlodipine, 5 mg or 10 mg, and Viagra, 100 mg were orally administered concomitantly to hypertensive patients mean additional blood pressure reduction of 8 mmHg systolic and 7 mmHg diastolic were noted [see Drug Interactions (7.3) and Clinical Pharmacology (12.2)].
Adverse Reactions with the Concomitant Use of Ritonavir
The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC). If Viagra is prescribed to patients taking ritonavir, caution should be used. Data from subjects exposed to high systemic levels of sildenafil are limited. Decreased blood pressure, syncope, and prolonged erection were reported in some healthy volunteers exposed to high doses of sildenafil (200–800 mg). To decrease the chance of adverse reactions in patients taking ritonavir, a decrease in sildenafil dosage is recommended [see Dosage and Administration (2.4), Drug Interactions (7.4), and Clinical Pharmacology (12.3)].
Combination with other PDE5 Inhibitors or Other Erectile Dysfunction Therapies
The safety and efficacy of combinations of Viagra with other PDE5 Inhibitors, including REVATIO or other pulmonary arterial hypertension (PAH) treatments containing sildenafil, or other treatments for erectile dysfunction have not been studied. Such combinations may further lower blood pressure. Therefore, the use of such combinations is not recommended.
Effects on Bleeding
There have been postmarketing reports of bleeding events in patients who have taken Viagra. A causal relationship between Viagra and these events has not been established. In humans, Viagra has no effect on bleeding time when taken alone or with aspirin. However, in vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). In addition, the combination of heparin and Viagra had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans.
The safety of Viagra is unknown in patients with bleeding disorders and patients with active peptic ulceration.
Counseling Patients About Sexually Transmitted Diseases
The use of Viagra offers no protection against sexually transmitted diseases. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered.