sildenafil (Rx)

>10%

Headache (7-16%)

1-10%

Flushing (4-10%)

Epistaxis (8%)

Dyspepsia (4-8%)

Insomnia (6%)

Erythema (5%)

Diarrhea (4%)

Dizziness (2%)

Skin rash (2%)

Postmarketing Reports

Vaso-occlusive crisis (PAH secondary to sickle-cell anemia)

Nonarteritic anterior ischemic optic neuropathy (NAION)

Contraindications

Hypersensitivity

Soluble guanylate cyclase (sGC) stimulators (eg, riociguat); concomitant use can cause hypotension

Coadministration with nitrates

• Coadministration with nitrates (either regularly and/or intermittently) and nitric oxide donors
• Consistent with the effects of PDE5 inhibition on the nitric oxide/cyclic guanosine monophosphate pathway, PDE5 inhibitors may potentiate the hypotensive effects of nitrates
• A suitable time interval following PDE5 dosing for the safe administration of nitrates or nitric oxide donors has not been determined

Cautions

Elicits vasodilatory properties, resulting in mild and transient decreases in blood pressure

Use with caution in patients with anatomic deformation of penis (eg, angulation, cavernosal fibrosis, or Peyronie disease), conditions potentially predisposing to priapism (eg, sickle cell anemia, multiple myeloma, or leukemia), cardiovascular disease, bleeding disorders, active peptic ulcer disease, liver disease, renal impairment, multidrug antihypertensive regimens, retinitis pigmentosa, concomitant use of CYP3A4 inhibitors

Pulmonary vasodilators may significantly worsen cardiovascular status of patients with pulmonary veno-occlusive disease

Patient taking alpha blocker should be stabilized before starting phosphodiesterase (PDE)-5 inhibitor, which should be initiated at lowest dose; if patient is already taking optimized dose of PDE-5 inhibitor, alpha blocker should be initated at lowest dose to avoid hypotension

Not to be taken with other PDE-5 inhibitors

Sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness

Viagra: Patients should stop sildenafil and seek medical care if a sudden loss of vision occurs in 1 or both eyes, which could be a sign of nonarteritic anterior ischemic optic neuropathy (NAION); use 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; advise patients to seek immediate medical attention in the event of a sudden loss of vision

Viagra: Potential for cardiac risk with sexual activity in patients with preexisting cardiovascular disease; therefore, treatment for erectile dysfunction generally should not be instituted in men for whom sexual activity is inadvisable because of their underlying cardiovascular status

May cause dose-related impairment of color discrimination; use caution in patients with retinitis pigmentosa

Evaluate underlying causes of erectile dysfunction or BPH before initiating therapy

Revatio: In small, prematurely terminated study of patients with PAH secondary to sickle-cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported by patients who received sildenafil than by those randomized to placebo; effectiveness of sildenafil in PAH secondary to sickle-cell anemia has not been established; the clinical relevance to men treated for erectile dysfunction with sildenafil is not known

Revatio: Not for use in children with PAH; increased mortality with increasing doses (hazard ratio 3.5) was observed in randomized, double-blind, placebo-controlled clinical trial of 234 children (1-17 years) with PAH who had mild-to-moderate symptoms at baseline

Revatio: Epistaxis occurred in 13% of patients with PAH secondary to connective tissue disease (eg, scleroderma); this effect was not seen in idiopathic PAH; incidence was also higher in those receiving concomitant PO vitamin K antagonist therapy (9%) than in those not receiving such therapy (2%)

Pregnancy

Limited published data from randomized controlled trials, case-controlled trials, and case series do not report a clear association with sildenafil and major birth defects, miscarriage, or adverse maternal or fetal outcomes when sildenafil is used during pregnancy; there are risks to mother and fetus from untreated pulmonary arterial hypertension

Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death

Lactation

Limited published data from a case report describe presence of sildenafil and its active metabolite in human milk; there is insufficient information about effects of sildenafil on breastfed infant and no information on effects of sildenafil on milk production; limited clinical data during lactation preclude a clear determination of risk of drug to an infant during lactation

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits PDE-5, increasing cyclic guanosine monophosphate cGMP to allow smooth-muscle relaxation

Absorption

Bioavailability: 40%

Peak plasma time: 30-120 min

Metabolism

Metabolized in liver by CYP3A4 and (in minor amounts) CYP2C9

Metabolites: N-desmethyl metabolite (active; possesses 50% of sildenafil's PDE-5-inhibiting activity)

Elimination

Half-life: Parent drug, 3-4 hr; active metabolite, 10-70 min

Excretion: Feces (80%), urine (13%)

IV Administration

Revatio: Administer as an IV bolus

Oral Administration

Viagra

• May take with or without food
• Take as needed, about 1 hr before sexual activity; however, may be taken anywhere from 30 minutes to 4 hr before sexual activity
• The maximum recommended dosing frequency is once daily

Revatio

• Tablets or oral suspension: Administer doses 4-6 hr apart

Storage

Revatio tablets or IV solution

• Store at controlled room temperature 20-25°C (68-77°F)
• Excursions permitted to 15-30°C (59-86°F)

Revatio reconstituted oral suspension

• Store <30°C (86°F) or in a refrigerator between 2-8°C (36-46°F)
• Do not freeze
• Discard unused oral suspension after 60 days