There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including VIAGRA (sildenafil citrate) , should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.

VIAGRA (sildenafil citrate) has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg), (see CLINICAL PHARMACOLOGY: Pharmacodynamics) While this normally would be expected to be of little consequence in most patients, prior to prescribing VIAGRA (sildenafil citrate) , physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity.

Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators including VIAGRA (sildenafil citrate) - those with left ventricular outflow obstruction (e.g. aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure.

There is no controlled clinical data on the safety or efficacy of VIAGRA (sildenafil citrate) in the following groups; if prescribed, this should be done with caution.

• Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months;
• Patients with resting hypotension (BP < 90/50) or hypertension (BP > 170/110);
• Patients with cardiac failure or coronary artery disease causing unstable angina;
• Patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of VIAGRA (sildenafil citrate) . In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.

The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC). If VIAGRA (sildenafil citrate) is prescribed to patients taking ritonavir, caution should be used. Data from subjects exposed to high systemic levels of sildenafil are limited. Visual disturbances occurred more commonly at higher levels of sildenafil exposure. 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 events in patients taking ritonavir, a decrease in sildenafil dosage is recommended (see DRUG INTERACTIONS, ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION)

General

The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment.

Before prescribing VIAGRA (sildenafil citrate) , it is important to note the following:

Caution is advised when Phosphodiesterase Type 5 (PDE5) inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including VIAGRA (sildenafil citrate) , 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 be anticipated. In some patients, concomitant use of these two drug classes can lower blood pressure significantly (see DRUG INTERACTIONS) leading to symptomatic hypotension (e.g. dizziness, lightheadedness, fainting).

Consideration should be given to 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 those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest dose.

- 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 (sildenafil citrate) has systemic vasodilatory properties and may augment the blood pressure lowering effect of other anti-hypertensive medications.

Patients on multiple antihypertensive medications were included in the pivotal clinical trials for VIAGRA (sildenafil citrate) . In a separate drug interaction study, when amlodipine, 5 mg or 10 mg, and VIAGRA (sildenafil citrate) , 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).

The safety of VIAGRA (sildenafil citrate) is unknown in patients with bleeding disorders and patients with active peptic ulceration.

VIAGRA (sildenafil citrate) should be used 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).

The safety and efficacy of combinations of VIAGRA (sildenafil citrate) with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.

In humans, VIAGRA (sildenafil citrate) has no effect on bleeding time when taken alone or with aspirin. In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). The combination of heparin and VIAGRA (sildenafil citrate) had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans.

Information for Patients

Physicians should discuss with patients the contraindication of VIAGRA (sildenafil citrate) with regular and/or intermittent use of organic nitrates.

Physicians should advise patients of the potential for VIAGRA (sildenafil citrate) to augment the blood pressure lowering effect of alpha-blockers and anti-hypertensive medications. Concomitant administration of VIAGRA (sildenafil citrate) and an alpha-blocker may lead to symptomatic hypotension in some patients. Therefore, when VIAGRA (sildenafil citrate) is co-administered with alpha-blockers, patients should be stable on alpha-blocker therapy prior to initiating VIAGRA (sildenafil citrate) treatment and VIAGRA (sildenafil citrate) should be initiated at the lowest dose.

Physicians should discuss with patients the potential cardiac risk of sexual activity in patients with preexisting cardiovascular risk factors. Patients who experience symptoms (e.g., angina pectoris, dizziness, nausea) upon initiation of sexual activity should be advised to refrain from further activity and should discuss the episode with their physician.

Physicians should advise patients to stop use of all PDE5 inhibitors, including VIAGRA (sildenafil citrate) , 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 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. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors. Physicians should also discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators, such as PDE5 inhibitors (see Post-Marketing Experience/Special Senses).

Physicians should advise patients to stop taking PDE5 inhibitors, including VIAGRA (sildenafil citrate) , 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 (sildenafil citrate) . 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, Clinical Trials and Post-Marketing Experience).

Physicians should warn patients that prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of VIAGRA (sildenafil citrate) . In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

Physicians should inform patients not to take VIAGRA (sildenafil citrate) with other PDE5 inhibitors including REVATIO. Sildenafil is also marketed as REVATIO for the treatment of pulmonary arterial hypertension. The safety and efficacy of VIAGRA (sildenafil citrate) with other PDE5 inhibitors, including REVATIO, have not been studied.

The use of VIAGRA (sildenafil citrate) 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 29- and 42-times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg. Sildenafil was not carcinogenic when administered to mice for 18-21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD on a mg/m² basis.

Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity.

There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC.

There was no effect on sperm motility or morphology after single 100 mg oral doses of VIAGRA (sildenafil citrate) in healthy volunteers.

Pregnancy, Nursing Mothers and Pediatric Use

VIAGRA (sildenafil citrate) is not indicated for use in newborns, children, or women.

Pregnancy Category B. No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received up to 200 mg/kg/day during organogenesis. These doses represent, respectively, about 20 and 40 times the MRHD on a mg/m² basis in a 50 kg subject. In the rat pre- and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days. In the nonpregnant rat the AUC at this dose was about 20 times human AUC. There are no adequate and well-controlled studies of sildenafil in pregnant women.

Geriatric Use: Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil (see CLINICAL PHARMACOLOGY: Pharmacokinetics in Special Populations). Since higher plasma levels may increase both the efficacy and incidence of adverse events, a starting dose of 25 mg should be considered (see DOSAGE AND ADMINISTRATION).

Last reviewed on RxList: 1/3/2011
This monograph has been modified to include the generic and brand name in many instances.