Sildenafil (Erectile Dysfunction) (Monograph)

Brand name: Viagra
Drug class: Phosphodiesterase Type 5 Inhibitors

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Vasodilating agent; a selective phosphodiesterase (PDE) type 5 inhibitor.

Uses for Sildenafil (Erectile Dysfunction)

Erectile Dysfunction (ED)

Used for the treatment of erectile dysfunction (ED, impotence).

Experts recommend a selective PDE type 5 inhibitor as first-line therapy for ED unless contraindicated. Evidence currently insufficient to support the superiority of one selective PDE type 5 inhibitor over another.

Sildenafil (Erectile Dysfunction) Dosage and Administration

Administration

Oral Administration

Administer orally about 1 hour (range: 4 hours to 30 minutes) before sexual activity.

Administration with a high-fat meal may delay the onset of action.

Sexual stimulation is required for response to therapy.

Dosage

Available as sildenafil citrate; dosage expressed in terms of sildenafil.

Adults

ED

Oral

Initially, 50 mg as a single dose as needed no more than once daily.

Depending on effectiveness and tolerance, increase dosage to a maximum of 100 mg once daily or decrease to 25 mg once daily.

Dosage Modifications for Drug Interactions

α-Adrenergic Blocking Agent: Patients should be stable on the α-adrenergic blocking agent before initiating sildenafil; initiate sildenafil at the lowest dose.

CYP3A4 Inhibitors:Strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, cobicistat) or the moderate CYP3A4 inhibitor erythromycin: Initial recommended dose of sildenafil is 25 mg.

Protease Inhibitors (e.g., Ritonavir):Do not exceed a maximum single sildenafil dose of 25 mg in a 48 hour period.

Special Populations

Hepatic Impairment

Reduce initial dose to 25 mg.

Renal Impairment

Cl_cr <30 mL/minute: reduce initial dose to 25 mg.

Geriatric Patients

Reduce initial dose to 25 mg in men ≥65 years of age.

Cautions for Sildenafil (Erectile Dysfunction)

Contraindications

Hypersensitivity to sildenafil.
Concomitant use of organic nitrates or nitrites in any form, either regularly or intermittently.
Concomitant use of guanylate cyclase stimulators (e.g., riociguat).

Warnings/Precautions

Cardiovascular Effects

Potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.

Use with caution in patients with a recent (within 6 months) MI, stroke, or life-threatening arrhythmia; in patients with resting hypotension (BP <90/50 mm Hg) or hypertension (BP >170/110 mm Hg); or in patients with cardiac failure or CAD causing unstable angina.

Consider whether patients with underlying cardiovascular disease (e.g., severe left ventricular outflow obstruction, autonomic dysfunction, resting hypotension [BP <90/50 mm Hg], fluid depletion) could be adversely affected by sildenafil’s vasodilatory activity, especially in combination with sexual activity.

Ocular Effects

Nonarteritic anterior ischemic optic neuropathy (NAION) reported rarely in patients receiving PDE type 5 inhibitors for the treatment of ED. Potential increased risk of NAION in the second eye in patients who already have had NAION in one eye.

If sudden vision loss or decreased vision occurs in one or both eyes, discontinue drug and contact a clinician immediately.

Use with caution in patients with retinitis pigmentosa.

Otic Effects

Sudden decrease or loss of hearing, with or without concomitant vestibular manifestations (e.g., tinnitus, vertigo, dizziness) reported with all PDE type 5 inhibitors, including sildenafil.

Not clear whether such effects are directly related to PDE type 5 inhibitors or to other underlying risk factors for hearing loss, a combination of these factors, or to other factors.

Discontinue sildenafil and seek medical attention immediately if sudden hearing loss or decreased hearing occurs.

Priapism

Possible prolonged (>4 hours) erections and priapism (painful erection >6 hours).

May result in penile tissue damage and permanent loss of potency if priapism is not treated immediately.

Use with caution in patients with anatomic deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie's disease) and conditions predisposing to priapism (e.g., sickle cell anemia, multiple myeloma, leukemia).

Concomitant Administration with α-Adrenergic Blocking Agents

Use with caution in patients receiving α-adrenergic blocking agents; possible potentiation of hypotensive effects due to additive vasodilatory action. In some cases, dose adjustments necessary; in other cases, concomitant administration not recommended.

In patients who exhibit hemodynamic instability while receiving an α-adrenergic blocking agent, use caution. Patients should be stable on an α-adrenergic blocking agent prior to initiation of sildenafil, and sildenafil should be administered at the lowest possible dose. In patients receiving an optimal dose of sildenafil, initiate the α-adrenergic blocking agent at the lowest dose.

Concomitant Use with Ritonavir

Concomitant administration of ritonavir substantially increases serum concentrations of sildenafil; decreased BP, syncope, and prolonged erection reported.

Use caution; reduce sildenafil dosage to decrease risk of adverse reactions.

Bleeding

Use with caution in patients with bleeding disorders or active peptic ulcers.

Combination with other PDE Type 5 Inhibitors or other ED Therapies

Safety and efficacy not established for use in combination with other PDE type 5 inhibitors or other treatments for ED; such combinations may further lower BP and not recommended.

Counseling Patients about Sexually Transmitted Diseases

Use of sildenafil provides no protection against sexually transmitted diseases; counsel patients regarding protective measures to guard against such transmission.

Specific Populations

Pregnancy

Not indicated for use in females. No data in pregnant women to inform any drug-associated risks for adverse developmental outcomes.

No evidence of teratogenicity, embryotoxicity, or fetotoxicity in animal studies.

Lactation

Not indicated for use in females.

Limited data indicate that sildenafil and its active metabolite are present in human milk.

No data on effects on the breastfed infant or on milk production.

Females and Males of Reproductive Potential

No evidence of impaired fertility in animal studies.

No effect on sperm motility of morphology in healthy human adults.

Pediatric Use

Not indicated for use in pediatric patients. Safety and efficacy not established in children.

Geriatric Use

No overall differences in safety and efficacy between geriatric (≥65 years of age) and younger patients.

Decreased clearance and increased plasma concentrations may increase incidence of adverse effects in geriatric patients.

Hepatic Impairment

Child-Pugh class A or B: Decreased clearance. Pharmacokinetics in patients with severe hepatic impairment (Child-Pugh class C): Not studied. Starting dose of 25 mg should be considered in patients with any degree of hepatic impairment.

Renal Impairment

Pharmacokinetics not altered in patients with mild or moderate (Cl_cr30–80 mL/minute) renal impairment.

Decreased clearance in patients with severe (Cl_cr<30 mL/minute) renal impairment; consider reducing initial dose to 25 mg.

Common Adverse Effects

Common adverse effects (≥2%): headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, rash.

Drug Interactions

Metabolized principally by CYP3A4 and to some extent by CYP2C9; weakly inhibits CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4 and CYP2C9: Potential pharmacokinetic interaction (increased plasma sildenafil concentrations).

Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma sildenafil concentrations).

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4: sildenafil not expected to alter pharmacokinetics of substrate drug.

Specific Drugs

Drug	Interaction	Comments
α-Adrenergic blockers	Possible potentiation of systemic vasodilation and symptomatic hypotension	In patients stable on an α-adrenergic blocker, initiate sildenafil at lowest recommended dosage for treatment of ED; in those currently receiving sildenafil, initiate α-adrenergic blocker at the lowest dosage Use concomitantly with caution
Alcohol	No additive hypotensive effects reported
Antacids	Oral bioavailability of sildenafil unaffected by single doses of aluminum and magnesium hydroxide-containing antacid
Antidepressants (e.g., SSRIs, tricyclic antidepressants)	No effect on sildenafil pharmacokinetics No change in efficacy of sildenafil for treatment of ED
Antifungals, azole (itraconazole, ketoconazole)	Possible increased systemic exposure of sildenafil	Consider lower initial sildenafil dose (25 mg) for treatment of ED
Antihypertensive and hypotensive agents	Potential additive hypotensive effects Amlodipine: Additional reductions in supine BP observed Thiazides and related diuretics, ACE inhibitors, calcium channel-blocking agents: No effect on sildenafil pharmacokinetics Loop and potassium-sparing diuretics, nonspecific β-adrenergic blocking agents: Increased AUC of active sildenafil metabolite (N-desmethyl sildenafil), but effect not expected to be clinically important
Antiretroviral agents (HIV protease inhibitors, alone or in combination with ritonavir)	Decreased clearance, increased plasma concentrations of sildenafil, and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)	Reduce initial sildenafil dose for treatment of ED to 25 mg and do not exceed a single 25-mg dose every 48 hours
Antiretroviral agents (nonnucleoside reverse transcriptase inhibitors [NNRTIs])	Etravirine: Decreased plasma sildenafil concentrations	May administer concomitantly without dosage adjustment, but increase in sildenafil dosage may be needed based on clinical effect
Aspirin	No increase in bleeding time reported
Bosentan	Decreased plasma sildenafil concentrations; increased plasma bosentan concentrations Clinical importance of pharmacokinetic interaction unclear
Cimetidine	Increased plasma sildenafil concentrations	Consider lower initial sildenafil dose (25 mg) for treatment of ED
Cobicistat in combination with elvitegravir	Increased plasma sildenafil concentrations expected	Reduce sildenafil dose to 25 mg and do not exceed a single 25-mg dose every 48 hours
Heparin	Increased bleeding time reported in animals	Current evidence does not preclude concomitant heparin
Inhaled nitrites (e.g., amyl or butyl nitrite)	Possible sudden and marked BP reduction; potentially serious or even fatal	Concomitant use contraindicated
Macrolides (azithromycin, erythromycin)	Azithromycin: No pharmacokinetic interaction observed to date Erythromycin: Increased AUC of sildenafil	Azithromycin: No dosage adjustments necessary Erythromycin: Consider lower initial sildenafil dose (25 mg)
Nitrates and nitrites (e.g., nitroglycerin, isosorbide dinitrate)	Potentiation of vasodilatory effects (e.g., decrease in systolic BP of >25 mm Hg) of organic nitrates and nitrites; potentially life-threatening hypotension and/or hemodynamic compromise can result	Concomitant use contraindicated Some clinicians suggest that nitrates and nitrites may be given >24 hours after sildenafil, but the point at which these drugs can be given safely after sildenafil is unclear; avoid concomitant use unless benefits outweigh risks
PDE inhibitors	Safety and efficacy of concomitant use not evaluated	Combination therapy not recommended
Rifamycins (rifabutin, rifampin)	Possible decreased plasma sildenafil concentrations
Riociguat	Possible additive hypotensive effects	Concomitant use contraindicated
Sodium nitroprusside	Potentiation of vasodilatory effects (e.g., decrease in systolic BP of >25 mm Hg) of organic nitrates and nitrites; potentially life-threatening hypotension and/or hemodynamic compromise can result Also may potentiate the inhibitory effect of nitric oxide and sodium nitroprusside (a nitric oxide donor) on platelet aggregation	Concomitant use contraindicated Some clinicians suggest that nitrates and nitrites may be given >24 hours after sildenafil, but the point at which these drugs can be given safely after sildenafil is unclear; avoid concomitant use unless benefits outweigh risks
Tolbutamide	No effect on sildenafil pharmacokinetics
Vitamin K antagonists (e.g., acenocoumarol, phenprocoumon, warfarin)	No substantial effect on INR; Warfarin: No pharmacokinetic interaction observed

Sildenafil (Erectile Dysfunction) Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; mean absolute bioavailability 41% (range, 25–63%).

Peak plasma concentrations usually attained within 30–120 minutes.

Duration

Erectile responsiveness: Approximately 2 hours.

Onset

Erectile responsiveness: 14–20 minutes, self-recorded in the home setting.

Food

Administration with a high-fat meal delays GI absorption; peak plasma concentrations reduced by about 30% and time to peak plasma concentrations delayed by about 60 minutes.

Distribution

Extent

Appears to be widely distributed in the body.

Distributed to a limited extent in semen, but such concentrations are unlikely to cause any effects in sexual partners.

Plasma Protein Binding

Approximately 96%.

Elimination

Metabolism

Undergoes extensive metabolism in GI mucosa during absorption and on first pass through liver.

Metabolized in the liver principally by CYP3A4 and to a lesser extent by CYP2C9.

N-desmethtyl metabolite accounts for about 20% of pharmacologic activity.

Elimination Route

Excreted as metabolites in the feces (approximately 80%) and urine (approximately 13%).

Half-life

Biphasic; terminal elimination half-life about 4 hours.

Special Populations

Clearance in patients ≥65 years of age is reduced compared with that in younger adults.

In patients with severe renal impairment (Cl_cr <30 mL/minute), clearance was reduced resulting in a two-fold increase in AUC and peak plasma concentrations compared with values in healthy adults. Pharmacokinetics not altered in mild to moderate renal impairment.

Reduced clearance in patients with hepatic cirrhosis (Child-Pugh class A or B).

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).

Actions

Selective inhibitor of PDEs, with greatest selectivity for PDE type 5, the principal isoenzyme involved in the metabolism of cGMP to GMP in the corpora cavernosa of the penis.
No direct relaxant effect on isolated human corpora cavernosa of the penis, but enhances the effect of nitric oxide by inhibiting PDE type 5-mediated hydrolysis of cGMP.
Potentiates accumulation of cGMP only when cGMP production in the penis is increased by sexual arousal. No effect on erectile function in the absence of sexual stimulation.
Modest peripheral vasodilation at usual dosages. Vasodilation and decreases in BP probably result from inhibition of PDE type 5 present in vascular smooth muscle.

Advice to Patients

Instruct patients to read the manufacturer's patient information before starting sildenafil therapy and each time their prescription is refilled.
Instruct patients to avoid contraindicated medications such as regular and/or intermittent use of organic nitrates, organic nitrites (e.g., “poppers”), and riociguat.
Inform patients that sildenafil is marketed for ED (Viagra) and pulmonary arterial hypertension (Revatio). Advise patients taking Viagra not to take Revatio or other PDE type 5 inhibitors.
Advise patients of the potential for sildenafil to augment the blood pressure lowering effect of α-adrenergic blocking agents (e.g., doxazosin) and anti-hypertensive medications (e.g., amlodipine) and that concomitant administration may lead to symptomatic hypotension in some patients. When sildenafil is co-administered with α-adrenergic blocking agents, patients should be stable on α-adrenergic blocking agent therapy prior to initiating treatment and sildenafil should be initiated at the lowest dose.
Inform patients taking sildenafil for ED and with potential for cardiac risk of sexual activity (e.g., patients with preexisting cardiovascular risk factors) to refrain from further activity and seek medical attention immediately if they experience symptoms (e.g., chest pain, dizziness, nausea) upon initiation of sexual activity.
Advise patients to seek immediate medical attention for a sudden loss of vision in one or both eyes while taking sildenafil. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including possible permanent loss of vision.
Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking sildenafil. These events may be accompanied by tinnitus and dizziness.
Advise patients to seek prompt medical attention for an erection that lasts more than 4 hours. If it is not treated right away, priapism can permanently damage the penis.
Inform patients taking sildenafil for ED that the drug offers no protection against sexually transmitted diseases and patients should use necessary protective measures to guard against such diseases, including HIV.
Instruct the patient to seek medical attention immediately if they take too much sildenafil.
Inform patients of the risk of symptomatic low BP (e.g., dizziness, lightheadedness, fainting). Monitor BP when administering sildenafil in combination with BP-reducing drugs (e.g., α-adrenergic blocking agents).
Advise patients to take sildenafil with or without food 1 hour or, if needed, 30 minutes to 4 hours before sexual activity. Inform patients that taking sildenafil with a high-fat meal may cause delayed onset. Do not take sildenafil more than 1 time a day.
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Sildenafil Citrate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	25 mg (of sildenafil)*	Sildenafil Tablets
			Viagra	Pfizer
		50 mg (of sildenafil)*	Sildenafil Tablets
			Viagra	Pfizer
		100 mg (of sildenafil)*	Sildenafil Tablets
			Viagra	Pfizer