Sildenafil (Erectile Dysfunction) (Monograph)
Brand name: Viagra
Drug class: Calcium-Channel Blocking Agents
Introduction
Vasodilating agent; a selective phosphodiesterase (PDE) type 5 inhibitor.1 2 4 5 7 8 10 24 27 33 41 56 57 67 91 131
Uses for Sildenafil (Erectile Dysfunction)
Erectile Dysfunction (ED)
Used for the treatment of erectile dysfunction (ED, impotence).1 4 6 7 8 9 10 25 33 34 67 81 102 104 105 107 108 112 118 126 127 128 129 130 131 132 133 134 140 142 143 144 189
Experts recommend a selective PDE type 5 inhibitor as first-line therapy for ED unless contraindicated.189 601 Evidence currently insufficient to support the superiority of one selective PDE type 5 inhibitor over another.189 601 602
Related/similar drugs
tadalafil, sildenafil, Cialis, Viagra, Adcirca, alprostadil, Levitra
Sildenafil (Erectile Dysfunction) Dosage and Administration
Administration
Oral Administration
Administer orally about 1 hour (range: 4 hours to 30 minutes) before sexual activity.1 91 127 132
Administration with a high-fat meal may delay the onset of action.1 117 131 602 603
Sexual stimulation is required for response to therapy.1
Dosage
Available as sildenafil citrate; dosage expressed in terms of sildenafil.1 203
Adults
ED
Oral
Initially, 50 mg as a single dose as needed no more than once daily.1 28 33 81 91 93 94 102 105 118 130 132 161
Depending on effectiveness and tolerance, increase dosage to a maximum of 100 mg once daily or decrease to 25 mg once daily.1 28 33 91 93 94 105 161
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.1
CYP3A4 Inhibitors:Strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, cobicistat) or the moderate CYP3A4 inhibitor erythromycin: Initial recommended dose of sildenafil is 25 mg.1 200
Protease Inhibitors (e.g., Ritonavir):Do not exceed a maximum single sildenafil dose of 25 mg in a 48 hour period.1
Special Populations
Hepatic Impairment
Reduce initial dose to 25 mg.1
Renal Impairment
Clcr <30 mL/minute: reduce initial dose to 25 mg.1
Geriatric Patients
Reduce initial dose to 25 mg in men ≥65 years of age.1
Cautions for Sildenafil (Erectile Dysfunction)
Contraindications
-
Hypersensitivity to sildenafil.1
-
Concomitant use of organic nitrates or nitrites in any form, either regularly or intermittently.1
-
Concomitant use of guanylate cyclase stimulators (e.g., riociguat).1 247
Warnings/Precautions
Cardiovascular Effects
Potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease.1 Generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.1
Use with caution in patients with a recent (within 6 months) MI, stroke, or life-threatening arrhythmia;1 31 101 127 144 154 155 159 in patients with resting hypotension (BP <90/50 mm Hg) or hypertension (BP >170/110 mm Hg);1 31 101 127 144 154 155 159 or in patients with cardiac failure or CAD causing unstable angina.1 31 101 127 144 154 155 159
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.1 67 154
Ocular Effects
Nonarteritic anterior ischemic optic neuropathy (NAION) reported rarely in patients receiving PDE type 5 inhibitors for the treatment of ED.1 190 191 192 196 197 Potential increased risk of NAION in the second eye in patients who already have had NAION in one eye.1 196
If sudden vision loss or decreased vision occurs in one or both eyes, discontinue drug and contact a clinician immediately.1
Use with caution in patients with retinitis pigmentosa.1 31 155
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.1
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.1
Discontinue sildenafil and seek medical attention immediately if sudden hearing loss or decreased hearing occurs.1
Priapism
Possible prolonged (>4 hours) erections and priapism (painful erection >6 hours).1 31 139 146 147
May result in penile tissue damage and permanent loss of potency if priapism is not treated immediately.1 31
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).1 33 159
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.1 In some cases, dose adjustments necessary; in other cases, concomitant administration not recommended.1
In patients who exhibit hemodynamic instability while receiving an α-adrenergic blocking agent, use caution.1 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.1 In patients receiving an optimal dose of sildenafil, initiate the α-adrenergic blocking agent at the lowest dose.1
Concomitant Use with Ritonavir
Concomitant administration of ritonavir substantially increases serum concentrations of sildenafil; decreased BP, syncope, and prolonged erection reported.1
Use caution; reduce sildenafil dosage to decrease risk of adverse reactions.1
Bleeding
Use with caution in patients with bleeding disorders or active peptic ulcers.1 27 33 67 131
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.1
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.1 26 68
Specific Populations
Pregnancy
Not indicated for use in females.1 No data in pregnant women to inform any drug-associated risks for adverse developmental outcomes.1
No evidence of teratogenicity, embryotoxicity, or fetotoxicity in animal studies.1
Lactation
Not indicated for use in females.1
Limited data indicate that sildenafil and its active metabolite are present in human milk.1
No data on effects on the breastfed infant or on milk production.1
Females and Males of Reproductive Potential
No evidence of impaired fertility in animal studies.1
No effect on sperm motility of morphology in healthy human adults.1
Pediatric Use
Not indicated for use in pediatric patients.1 Safety and efficacy not established in children.1
Geriatric Use
No overall differences in safety and efficacy between geriatric (≥65 years of age) and younger patients.1
Decreased clearance and increased plasma concentrations may increase incidence of adverse effects in geriatric patients.1
Hepatic Impairment
Child-Pugh class A or B: Decreased clearance.1 31 67 69 Pharmacokinetics in patients with severe hepatic impairment (Child-Pugh class C): Not studied.1 Starting dose of 25 mg should be considered in patients with any degree of hepatic impairment.1
Renal Impairment
Pharmacokinetics not altered in patients with mild or moderate (Clcr30–80 mL/minute) renal impairment.1
Decreased clearance in patients with severe (Clcr<30 mL/minute) renal impairment; consider reducing initial dose to 25 mg.1 67 80
Common Adverse Effects
Common adverse effects (≥2%): headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, rash.1
Drug Interactions
Metabolized principally by CYP3A4 and to some extent by CYP2C9; weakly inhibits CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4.1 26 67 91 250
Drugs Affecting Hepatic Microsomal Enzymes
Inhibitors of CYP3A4 and CYP2C9: Potential pharmacokinetic interaction (increased plasma sildenafil concentrations).1 26 67 91
Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma sildenafil concentrations).1 26 67 91 212
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4: sildenafil not expected to alter pharmacokinetics of substrate drug.1 26 67
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
α-Adrenergic blockers |
Possible potentiation of systemic vasodilation and symptomatic hypotension1 |
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 1 Use concomitantly with caution1 |
Alcohol |
No additive hypotensive effects reported1 |
|
Antacids |
Oral bioavailability of sildenafil unaffected by single doses of aluminum and magnesium hydroxide-containing antacid1 |
|
Antidepressants (e.g., SSRIs, tricyclic antidepressants) |
No effect on sildenafil pharmacokinetics1 No change in efficacy of sildenafil for treatment of ED1 |
|
Antifungals, azole (itraconazole, ketoconazole) |
Consider lower initial sildenafil dose (25 mg) for treatment of ED1 67 |
|
Antihypertensive and hypotensive agents |
Potential additive hypotensive effects1 29 67 Amlodipine: Additional reductions in supine BP observed1 29 154 Thiazides and related diuretics, ACE inhibitors, calcium channel-blocking agents: No effect on sildenafil pharmacokinetics1 Loop and potassium-sparing diuretics, nonspecific β-adrenergic blocking agents: Increased AUC of active sildenafil metabolite (N-desmethyl sildenafil),1 but effect not expected to be clinically important1 |
|
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)1 26 67 139 200 240 |
Reduce initial sildenafil dose for treatment of ED to 25 mg and do not exceed a single 25-mg dose every 48 hours1 200 240 |
Antiretroviral agents (nonnucleoside reverse transcriptase inhibitors [NNRTIs]) |
Etravirine: Decreased plasma sildenafil concentrations200 |
May administer concomitantly without dosage adjustment, but increase in sildenafil dosage may be needed based on clinical effect200 |
Aspirin |
||
Bosentan |
Decreased plasma sildenafil concentrations; increased plasma bosentan concentrations1 241 212 Clinical importance of pharmacokinetic interaction unclear241 |
|
Cimetidine |
Consider lower initial sildenafil dose (25 mg) for treatment of ED67 |
|
Cobicistat in combination with elvitegravir |
Increased plasma sildenafil concentrations expected200 |
Reduce sildenafil dose to 25 mg and do not exceed a single 25-mg dose every 48 hours200 |
Heparin |
Increased bleeding time reported in animals1 |
Current evidence does not preclude concomitant heparin67 |
Inhaled nitrites (e.g., amyl or butyl nitrite) |
Possible sudden and marked BP reduction; potentially serious or even fatal26 67 |
|
Macrolides (azithromycin, erythromycin) |
Azithromycin: No pharmacokinetic interaction observed to date138 239 |
Azithromycin: No dosage adjustments necessary 239 Erythromycin: Consider lower initial sildenafil dose (25 mg)1 239 |
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 result1 28 29 31 33 53 57 61 67 69 91 127 131 148 |
Concomitant use contraindicated1 29 57 67 148 154 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;1 29 31 67 154 avoid concomitant use unless benefits outweigh risks67 |
PDE inhibitors |
Safety and efficacy of concomitant use not evaluated1 |
Combination therapy not recommended1 |
Rifamycins (rifabutin, rifampin) |
||
Riociguat |
||
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 result1 28 29 31 33 53 57 61 67 69 91 127 131 148 Also may potentiate the inhibitory effect of nitric oxide and sodium nitroprusside (a nitric oxide donor) on platelet aggregation1 57 67 |
Concomitant use contraindicated1 29 57 67 148 154 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;1 29 31 67 154 avoid concomitant use unless benefits outweigh risks67 |
Tolbutamide |
||
Vitamin K antagonists (e.g., acenocoumarol, phenprocoumon, warfarin) |
Sildenafil (Erectile Dysfunction) Pharmacokinetics
Absorption
Bioavailability
Rapidly absorbed following oral administration;1 4 56 67 91 116 203 mean absolute bioavailability 41% (range, 25–63%).1 4 56 67 91 116 131
Peak plasma concentrations usually attained within 30–120 minutes.1 4 91 127 130
Duration
Erectile responsiveness: Approximately 2 hours.1
Onset
Erectile responsiveness: 14–20 minutes, self-recorded in the home setting.178
Food
Administration with a high-fat meal delays GI absorption;1 131 peak plasma concentrations reduced by about 30% and time to peak plasma concentrations delayed by about 60 minutes.1 131
Distribution
Extent
Appears to be widely distributed in the body.1 4 67 116 131
Distributed to a limited extent in semen,1 67 but such concentrations are unlikely to cause any effects in sexual partners.67
Plasma Protein Binding
Approximately 96%.1 67 91 116 131
Elimination
Metabolism
Undergoes extensive metabolism in GI mucosa during absorption and on first pass through liver.91 116
Metabolized in the liver 116 131 principally by CYP3A4 and to a lesser extent by CYP2C9.1 91 131
N-desmethtyl metabolite accounts for about 20% of pharmacologic activity.1
Elimination Route
Excreted as metabolites in the feces (approximately 80%) and urine (approximately 13%).1 67 116 131
Half-life
Biphasic; terminal elimination half-life about 4 hours.1 4 67 91 116 127 130 131
Special Populations
Clearance in patients ≥65 years of age is reduced compared with that in younger adults.1 31 67 91 131 139
In patients with severe renal impairment (Clcr <30 mL/minute), clearance was reduced resulting in a two-fold increase in AUC and peak plasma concentrations compared with values in healthy adults.1 31 67 91 131 139 Pharmacokinetics not altered in mild to moderate renal impairment.1 31 131
Reduced clearance in patients with hepatic cirrhosis (Child-Pugh class A or B).1 31 131
Stability
Storage
Oral
Tablets
25°C (may be exposed to 15–30°C).1
Actions
-
Selective inhibitor of PDEs, with greatest selectivity for PDE type 5,1 2 4 5 7 8 10 24 27 33 41 56 57 67 87 88 91 131 the principal isoenzyme involved in the metabolism of cGMP to GMP in the corpora cavernosa of the penis.1 2 4 5 33 41 42 54 57 67 91 131
-
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.1 2 4 5 7 8 10 33 41 42 127 131
-
Potentiates accumulation of cGMP only when cGMP production in the penis is increased by sexual arousal.34 91 131 No effect on erectile function in the absence of sexual stimulation.1 4 33 34 91 127 130 131 132
-
Modest peripheral vasodilation at usual dosages.1 29 31 33 53 56 67 91 Vasodilation and decreases in BP probably result from inhibition of PDE type 5 present in vascular smooth muscle.1 27 31 53
Advice to Patients
-
Instruct patients to read the manufacturer's patient information before starting sildenafil therapy and each time their prescription is refilled.1
-
Instruct patients to avoid contraindicated medications such as regular and/or intermittent use of organic nitrates, organic nitrites (e.g., “poppers”), and riociguat.1
-
Inform patients that sildenafil is marketed for ED (Viagra) and pulmonary arterial hypertension (Revatio).1 Advise patients taking Viagra not to take Revatio or other PDE type 5 inhibitors.1
-
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.1 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.1
-
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.1
-
Advise patients to seek immediate medical attention for a sudden loss of vision in one or both eyes while taking sildenafil.1 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.1
-
Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking sildenafil.1 These events may be accompanied by tinnitus and dizziness.1
-
Advise patients to seek prompt medical attention for an erection that lasts more than 4 hours.1 If it is not treated right away, priapism can permanently damage the penis.1
-
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.1
-
Instruct the patient to seek medical attention immediately if they take too much sildenafil.1
-
Inform patients of the risk of symptomatic low BP (e.g., dizziness, lightheadedness, fainting).1 Monitor BP when administering sildenafil in combination with BP-reducing drugs (e.g., α-adrenergic blocking agents).1
-
Advise patients to take sildenafil with or without food 1 hour or, if needed, 30 minutes to 4 hours before sexual activity.1 Inform patients that taking sildenafil with a high-fat meal may cause delayed onset.1 Do not take sildenafil more than 1 time a day.1
-
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
-
Inform patients of other important precautionary information.1
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
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 |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
References
1. Pfizer Inc. Viagra (sildenafil citrate) prescribing information. New York, NY; 2017 Dec.
2. Anon. Sildenafil. Drugs Future. 1997; 22:138-43.
4. Boolell M, Allen MJ, Ballard SA et al. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res. 1996; 8:47-52. http://www.ncbi.nlm.nih.gov/pubmed/8858389?dopt=AbstractPlus
5. Terrett NK, Bell AS, Brown D et al. Sildenafil (Viagra), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg Med Chem Lett. 1996; 6:1819-24.
6. Boolell M, Yates PK, Wulff MB et al. Sildenafil (Viagra), a novel oral treatment with rapid onset of action for penile erectile dysfunction. Int J Impot Res. 1996; 8:147.
7. Christiansen E and the Multicentre Study Group. Sildenafil (Viagra) a new oral treatment for erectile dysfunction (ED): results of a 16 week open dose escalation study. Int J Impot Res. 1996; 8:147.
8. Dinsmore WW, Gingell CJ, Jardin A et al. Sildenafil (Viagra), a new oral treatment for erectile dysfunction (ED), a double blind, placebo controlled, parallel goup, once daily dose reponse study. Int J Impot Res. 1996; 8:147.
9. Gingell CJC, Jardin A, Olsson AM et al et al. UK-92,480, a new oral treatment for erectile dysfunction: a double-blind, placebo-controlled, once daily dose response study. J Urol. 1996; 155(Suppl 5):495A.
10. Eardley I, Morgan RJ, DinsmoreWW et al. UK-92,480, a new oral therapy for erectile dysfunction, a double-blind, placebo controlled trial with treatment taken as required. J Urol. 1996; 155(Suppl 5):495A.
12. National Institutes of Health Office of Medical Applications of Research. Consensus Conference: impotence. JAMA. 1993; 270:83-90. http://www.ncbi.nlm.nih.gov/pubmed/8510302?dopt=AbstractPlus
24. Tang K, Turner LA, Ballard SA et al. Effects of the novel phosphodiesterase type 5 inhibitor, sildenafil, on methacholine-induced relaxation of rabbit isolated corpus cavernosum. Br J Pharmacol. 1996; 118(Suppl). Abstract No. 154P.
25. Boolell M, Pearson J, Gingell JC et al. Sildenafil (Viagra) is an efficacious oral therapy in diabetic patients with erectile dysfunction (ED). Int J Impot Res. 1996; 8:186.
26. Nandwani R, Goutlay Y. Possible interaction between sildenafil and HIV combination therapy. Lancet. 1999; 353:840.
27. Sonnenburg WK, Beavo JA. Cyclic GMP and regulation of cyclic nucleotide hydrolysis. Adv Pharmacol. 1994; 26:87-114. http://www.ncbi.nlm.nih.gov/pubmed/8038108?dopt=AbstractPlus
28. Kloner RA. Erectile dysfunction and sildenafil citrate and cardiologists. Am J Cardiol. 1999; 83:576-82. http://www.ncbi.nlm.nih.gov/pubmed/10073864?dopt=AbstractPlus
29. Webb DJ, Freestone S, Allen MJ et al. Sildenafil citrate and blood-presssure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol. 1999; 83:21c-8c. http://www.ncbi.nlm.nih.gov/pubmed/10078539?dopt=AbstractPlus
30. Conti CR, Pepine CJ, Sweeney M. Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease. Am J Cardiol. 1999; 83:29c-34c. http://www.ncbi.nlm.nih.gov/pubmed/10078540?dopt=AbstractPlus
31. Zusman RM, Morales A, Glasser DB et al. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol. 1999; 83:35c-44c. http://www.ncbi.nlm.nih.gov/pubmed/10078541?dopt=AbstractPlus
33. Goldstein I, Lue TF, Padma-Nathan H et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 338:1397-404. http://www.ncbi.nlm.nih.gov/pubmed/9580646?dopt=AbstractPlus
34. Utiger RD. A pill for impotence. N Engl J Med. 1998; 338:1458-9. http://www.ncbi.nlm.nih.gov/pubmed/9580654?dopt=AbstractPlus
41. Stief CG, Uckert S, Becker AJ et al. The effect of the specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo. J Urol. 1998; 159:1390-3. http://www.ncbi.nlm.nih.gov/pubmed/9507890?dopt=AbstractPlus
42. Jeremy JY, Ballard SA, Naylor AM et al. Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. Br J Urol. 1997; 79:958-63. http://www.ncbi.nlm.nih.gov/pubmed/9202566?dopt=AbstractPlus
44. Ballard SA, Burslem FMF, Gingell CJC et al. In vitor profile of UK-92,480, an inhibitor of cyclic GMP-specific phosphodiestrase 5 for the treatment of male erectile dysfunction. J Urol. 1996; 155:676A.
45. Beavo JA, Reifsnyder DH. Primary sequence of cyclic nucleotide phosphodietesterase isoenzymes and the design of selective inhibitors. Trends Pharmacol Sci. 1990; 11:150-5. http://www.ncbi.nlm.nih.gov/pubmed/2159198?dopt=AbstractPlus
52. Pittler SJ, Baehr W. The molecular genetics of retinal photoreceptor proteins involved in cGMP metabolism. Prog Clin Biol Res. 1991; 362:33-66. http://www.ncbi.nlm.nih.gov/pubmed/1672236?dopt=AbstractPlus
53. Pfizer. Dear doctor letter to emergency physicians regarding Viagra contraindication: concomitant administration of an organic nitrate. From FDA web site. 1998 May 22.
54. Murray KJ. Phosphodiesterase VA inhibitors. Drug News Perspectives. 1993; 150-6.
55. Beavo JA, conti M, Heaslip RJ. Multiple cyclic nucleotide phosphodiesterases. Mol Pharmacol. 1994; 46:399-405. http://www.ncbi.nlm.nih.gov/pubmed/7935318?dopt=AbstractPlus
56. Jackson G, Benjamin N, Jackson N et al. Effects of sildenafil citrate on human hemodynamics. Am J Cardiol. 1999; 83:13c-20c. http://www.ncbi.nlm.nih.gov/pubmed/10078538?dopt=AbstractPlus
57. Wallis RM, Corbin JD, Francis SH et al. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol. 1999; 83:3c-12c. http://www.ncbi.nlm.nih.gov/pubmed/10078537?dopt=AbstractPlus
61. Anon. Summary of reports of death in Viagra users received from marketing (late March) through mid-november 1998. From FDA web site.
65. Goldstein I, Rosen RC, Steers WD. Sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 339:701-2.
66. Meikle AW, Arver S. Sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 339:700-1. http://www.ncbi.nlm.nih.gov/pubmed/9729140?dopt=AbstractPlus
67. Cheitkin MD, Hutter AM, Brindis RG for the American College or Cardiology and American Heart Association. Technology and Practice Executive Committee [duplicate publication of Cheitkin MD, Hutter AM, Brindis RG for the American College or Cardiology and American Heart Association. ACC/AHA expert consensus document: use of sildenafil (viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999; 33:273-82.
68. Little WN, Park GT, Patton HM. Sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 339:700. http://www.ncbi.nlm.nih.gov/pubmed/9729138?dopt=AbstractPlus
69. Anon. Sildenafil: an oral drug for impotence. Med Lett Drugs Ther. 1998; 40:51-52. http://www.ncbi.nlm.nih.gov/pubmed/9599594?dopt=AbstractPlus
70. Rosen RC. Sildenafil: medical advance or media event? Lancet. 1998; 351:1599-600.
76. Steers WD. Meta-analysis of the efficacy of sildenafil (Viagra) in the treatment of severe erectile dysfunction. J Urol. 1998; 159(Suppl):238.
78. Garg RK, Khaishgi A, Dandona P. Is management of impotence with sildenafil changing clinical practice? Lancet. 1999; 353:375-6.
80. Martinez F, Maillet R, Legendre C et al. Acute myocardial infarction associated with sildenafil. Lancet. 1998; 352:1937. http://www.ncbi.nlm.nih.gov/pubmed/9863818?dopt=AbstractPlus
81. Standing Medical Advisory Committee, United Kingdom Department of Health. The use of sildenafil in the treatment of erectile dysfunction. London; November 9, 1998. From the United Kingdom Department of Health Web Site. https://www.gov.uk/government/organisations/department-of-health-and-social-care
83. Chan-Tack KM. Oral sildenafil in erectile dysfunction. Lancet. 1998; 352:1557. http://www.ncbi.nlm.nih.gov/pubmed/9820338?dopt=AbstractPlus
85. Kumar GN, Rodrigues AD, Buko AM et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J Pharmacol Exp Ther. 1996; 277:423-31. http://www.ncbi.nlm.nih.gov/pubmed/8613951?dopt=AbstractPlus
87. Zrenner E. No cause for alarm over retinal side-effects of sildenafil. Lancet. 1999; 353:340-1. http://www.ncbi.nlm.nih.gov/pubmed/9950434?dopt=AbstractPlus
88. Vobig MA, Klotz T, Staak M et al. Retinal side-effects of sildenafil. Lancet. 1999; 353:375. http://www.ncbi.nlm.nih.gov/pubmed/9950445?dopt=AbstractPlus
89. Sly MK, Eberhart RC, Prager MD. Anti-platelet action of nitric oxide and selective phosphodiesterase inhibitors. Shock. 1997; 8:115-8. http://www.ncbi.nlm.nih.gov/pubmed/9261901?dopt=AbstractPlus
91. Goldenberg MM. Safety and efficacy of sildenafil citrate in the treatment of male erectile dysfunction. Clin ther. 1998; 20:1033-48. http://www.ncbi.nlm.nih.gov/pubmed/9916601?dopt=AbstractPlus
93. Rendell MS, Rajfer J, Wicker PA et al. Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. JAMA. 1999; 281:421-6. http://www.ncbi.nlm.nih.gov/pubmed/9952201?dopt=AbstractPlus
94. Padma-Nathan H, Steers WD, Wicker PA. Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients. Int J Clin Pract. 1998; 52:375-80. http://www.ncbi.nlm.nih.gov/pubmed/9894373?dopt=AbstractPlus
101. Lipshultz LI, Kim ED. Treatment of erectile dysfunction in men with diabetes. JAMA. 1999; 281:465-6. http://www.ncbi.nlm.nih.gov/pubmed/9952210?dopt=AbstractPlus
102. Derry FA, Dinsmore WW, Fraser M et al. Efficacy and safety of oral sildenafil in men with erectile dysfunction caused by spinal cord injury. Neurology. 1998; 51:1629-33. http://www.ncbi.nlm.nih.gov/pubmed/9855514?dopt=AbstractPlus
104. Zippe CD, Kedia AW, Kedia K et al. Treatment of erectile dysfunction after radical prostatect omy with sildenafil citrate (Viagra). Urology. 1998; 52:963-6. http://www.ncbi.nlm.nih.gov/pubmed/9836537?dopt=AbstractPlus
105. Zelefsky MJ, McKee AB, Lee H et al. Efficacy of oral sildenafil in patients with erectile dysfunction after radiotherapy for carcinoma or the prostate. Urology. 1999; 53:775-8. http://www.ncbi.nlm.nih.gov/pubmed/10197855?dopt=AbstractPlus
107. Dinsmore WW, Hodges M, Hargreaves C et al. Sildenafil citrate (viagra) in erectile dysfunction: near nomralization in men with broad-spectrum erectile dysfunction compared to age-matched healthy control subjects. Urology. 1999; 53:800-5. http://www.ncbi.nlm.nih.gov/pubmed/10197860?dopt=AbstractPlus
108. Nurnberg HG, Lauriello J, Hensley PL et al. Sildenafil for iatrogenic serotonergic antidepressant medication-induced sexual dysfunction in 4 patients. J Clin Psychiatry. 1999; 60:33-5. http://www.ncbi.nlm.nih.gov/pubmed/10074875?dopt=AbstractPlus
112. Ashton AK, Bennerr RG. Sildenafil treatment of serotonin reuptake inhibitor-induced sexual dysfunction. J Clin Psychiatry. 1999; 60:194-5. http://www.ncbi.nlm.nih.gov/pubmed/10192597?dopt=AbstractPlus
116. Walker DK, Ackland MJ, James GC et al. Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog, and man. Xenobiotica. 1999; 29:297-310. http://www.ncbi.nlm.nih.gov/pubmed/10219969?dopt=AbstractPlus
117. Nichols DJ, Muirhead GJ, Harness JA. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol. 2002;53 Suppl 1(Suppl 1):5S-12S. doi: 10.1046/j.0306-5251.2001.00027.x. PMID: 11879254; PMCID: PMC1874258
118. Fava M, Rankin MA, Alpert JE et al. An open trial of oral sildenafil in antidepressant-induced sexual dysfunction. Psychother Psychosom. 1998; 67:328-31. http://www.ncbi.nlm.nih.gov/pubmed/9817955?dopt=AbstractPlus
126. Palmer JS, Kaplan WE, Firlit CF. Erectile dysfunction in spina bifida is treatable. Lancet. 1999; 354:125-6. http://www.ncbi.nlm.nih.gov/pubmed/10408490?dopt=AbstractPlus
127. Steers WD. Viagra—after one year. Urology. 1999; 54:12-7. http://www.ncbi.nlm.nih.gov/pubmed/10414719?dopt=AbstractPlus
128. Hackett G, Gingell JC. Long-term safety and efficacy after 2 years of viagra (sildenafil citrate) treatment of erectle dysfunction. J Urol. 1999; 161:214.
129. Merrick GS, Butler WM, Lief JH et al. Efficacy of sildenafil citrate in prostate brachytherapy patients with erectile dysfunction. Urology. 1999; 53:1112-6. http://www.ncbi.nlm.nih.gov/pubmed/10367837?dopt=AbstractPlus
130. Montorsi F, McDermott ED, Morgan R et al. Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies. Urology. 1999; 53:1011-8. http://www.ncbi.nlm.nih.gov/pubmed/10223498?dopt=AbstractPlus
131. Langtry HD, Markham A. Sildenafil: a review of its use in erectile dysfunction. Drugs. 1999; 57:967-89. http://www.ncbi.nlm.nih.gov/pubmed/10400408?dopt=AbstractPlus
132. Morales A, Gingell C, Collins M et al. Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. Int J Impotence Res. 1998; 10:69-74.
133. Prisant M, Brown M et al. Sildenafil citrate: well-tolerated by patients with erectile dysfunction taking concomitant antihypertensive therapy. Am J Hypertens. 1999; 12:37A.
134. Kloner R, Brown M et al. Safety of sildenafil citrate in men with erectile dysfunction taking multiple antihypertensive agents. Am J Hypertens. 1999; 12:37A.
136. Von Moltke LL, Greenblatt DJ, Grassi JM et al. Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. J Clin Pharmacol. 1998; 38:106-11. http://www.ncbi.nlm.nih.gov/pubmed/9549640?dopt=AbstractPlus
137. Eagling VA, Back DJ, Barry MG. Differential inhibition of cytochrome P450 isoforms by protease inhbitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol. 1997; 44:190-4. http://www.ncbi.nlm.nih.gov/pubmed/9278209?dopt=AbstractPlus
138. von Rosensteil NA, Adam D. Macrolide antibacterials. Drug interactions of clinical significance. Drug Saf. 1995; 13:105-22. http://www.ncbi.nlm.nih.gov/pubmed/7576262?dopt=AbstractPlus
139. Food and Drug Administration. Viagra (sildenafil citrate) tablets [June 18, 1999: Pfizer]. MedWatch drug labeling changes. Rockville, MD; June 1999. From FDA website. http://www.fda.gov/Safety/MedWatch/SafetyInformation
140. Boolell M, Gepi-Attee S, Gingell JC et al. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol. 1996; 78:257-61. http://www.ncbi.nlm.nih.gov/pubmed/8813924?dopt=AbstractPlus
142. Giuliano F, Hultling C, El Masry WS et al for the Sildenafil Study Group. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Ann Neurol. 1999; 46:15-21. http://www.ncbi.nlm.nih.gov/pubmed/10401776?dopt=AbstractPlus
143. Tur-Kaspa I, Segal S, Moffa F et al. Viagra for temporary erectile dysfunction during treatments with assisted reproductive technologies. Hum Reprod. 1999; 14:1783-4. http://www.ncbi.nlm.nih.gov/pubmed/10402389?dopt=AbstractPlus
144. Palmer BF. Sexual dysfunction in uremia. J Am Soc Nephrol. 1999; 10:1381-8. http://www.ncbi.nlm.nih.gov/pubmed/10361878?dopt=AbstractPlus
145. Meinhardt W, Kropman RF, Vermeij P. Comparative tolerability and efficacy of treatments for impotence. Drug Saf. 1999; 20:133-146. http://www.ncbi.nlm.nih.gov/pubmed/10082071?dopt=AbstractPlus
146. Chang CH, Hung CJ, Chian SS et al. Acute renal failure in a young man, 9 days after a 5-h persisting erection following Viagra: is there a causal relationship? Nephrol Dial Transplant. 1999; 14:2045-7. Letter.
147. Grossman EB. Temporal association between the ingestion of two consecutive doses of sildenafil 100 mg by a healthy subject and his presentation several days later with symptoms of acute renal failure which resolved without treatment. Nephrol Dial Transplant. 1999; 14:2047. http://www.ncbi.nlm.nih.gov/pubmed/10462303?dopt=AbstractPlus
148. Arora RR, Meilli L. Acute myocardial infarction after the use of sildenafil. N Engl J Med. 1999; 341:700.
154. Kloner RA, Zusman RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84:11-7N.
155. Padma-Nathan H. A new era in the treatment of erectile dysfunction. Am J Cardiol. 1999; 84:18-23N. http://www.ncbi.nlm.nih.gov/pubmed/10404845?dopt=AbstractPlus
159. Heart and Stroke Foundation of Canada and Canadian Cardiovascular Society. A statement on the use of sildenafil in the management of sexual dysfunction in patients with cardiovascular disease. Can J Cardiol. 1999; 15:396-9. http://www.ncbi.nlm.nih.gov/pubmed/10348610?dopt=AbstractPlus
160. Petak SM, Baskin HJ, Bergman DA. AACE clinical practice guidelines for the evaluation and treatment of hypogonadism in adult male patients. From American Association of Clinical Endocrinologists web site.
161. Guay AT, Spark RF, Bansal S, Cunningham GR, Goodman NF, Nankin HR, Petak SM, Perez JB; American Association of Clinical Endocrinologists Male Sexual Dysfunction Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of male sexual dysfunction: a couple's problem--2003 update. Endocr Pract. 2003 Jan-Feb;9(1):77-95. doi: 10.4158/EP.9.1.77. PMID: 12917096. https://www.endocrinepractice.org/article/S1530-891X(20)40332-5/fulltext
163. Steers W, Guay AT, Leriche A et al. Assessment of the efficacy and safety of Viagra (sildenafil citrate) in men with erectile dysfunction during long-term treatment. Int J Impot Res. 2001; 13:261-7. http://www.ncbi.nlm.nih.gov/pubmed/11890512?dopt=AbstractPlus
165. Steers WD. Tachyphylaxis and phosphodiesterase type 5 inhibitors. J Urol. 2002; 168: 207. http://www.ncbi.nlm.nih.gov/pubmed/12050542?dopt=AbstractPlus
178. Padma-Nathan H, Stecher VJ, Sweeney M, Orazem J, Tseng LJ, Deriesthal H. Minimal time to successful intercourse after sildenafil citrate: results of a randomized, double-blind, placebo-controlled trial. Urology. 2003 Sep;62(3):400-3. doi: 10.1016/s0090-4295(03)00567-3. PMID: 12946731.
189. Burnett AL, Nehra A, Breau RH, Culkin DJ, Faraday MM, Hakim LS, Heidelbaugh J, Khera M, McVary KT, Miner MM, Nelson CJ, Sadeghi-Nejad H, Seftel AD, Shindel AW. Erectile Dysfunction: AUA Guideline. J Urol. 2018 Sep;200(3):633-641. doi: 10.1016/j.juro.2018.05.004. Epub 2018 May 7. Erratum in: J Urol. 2022 Mar;207(3):743. PMID: 29746858.
190. Egan RA, Fraunfelder FW. Viagra and anterior ischemic optic neuropathy. Arch Ophthalmol. 2005; 123:709-10. http://www.ncbi.nlm.nih.gov/pubmed/15883302?dopt=AbstractPlus
191. Anon. Viagra and loss of vision. Med Lett Drugs Ther. 2005; 47:49.
192. Egan R, Pomeranz H. Sildenafil (Viagra) associated anterior ischemic optic neuropathy. Arch Ophthalmol. 2000; 118:291-2. http://www.ncbi.nlm.nih.gov/pubmed/10676804?dopt=AbstractPlus
196. Bollinger KL, Lee MS. Recurrent visual field defect and ischemic optic neuropathy assciated with tadalafil rechallenge. Arch Ophthalmol. 2005; 123:400-1. http://www.ncbi.nlm.nih.gov/pubmed/15767488?dopt=AbstractPlus
197. Escaravage GK, Wright JD, Givre SJ. Tadalafil associated with anterior ischemic optic neuropathy. Arch Ophthalmol. 2005; 123:399-400. http://www.ncbi.nlm.nih.gov/pubmed/15767487?dopt=AbstractPlus
200. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services (Jan 20, 2022). Available at HIV.gov. https://clinicalinfo.hiv.gov/en/guidelines
203. Pfizer. Revatio (sildenafil citrate) tablets for oral use, oral suspension, and injection for intravenous use prescribing information. New York, NY; 2014 Mar.
212. Paul GA, Gibbs SR, Boobis AR et al. Bosentan decreases the plasma concentration of sildenafil when coprescibed in pulmonary hypertension. Br J Clin Pharmacol. 2005; 60:107-12. http://www.ncbi.nlm.nih.gov/pubmed/15963102?dopt=AbstractPlus
239. Muirhead GJ, Faulkner S, Harness JA et al. The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers. Br J Clin Pharmacol. 2002; 53 Suppl 1:37S-43S. http://www.ncbi.nlm.nih.gov/pubmed/11879258?dopt=AbstractPlus
240. Muirhead GJ, Wulff MB, Fielding A et al. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir. Br J Clin Pharmacol. 2000; 50:99-107. http://www.ncbi.nlm.nih.gov/pubmed/10930961?dopt=AbstractPlus
241. Burgess G, Hoogkamer H, Collings L et al. Mutual pharmacokinetic interactions between steady-state bosentan and sildenafil. Eur J Clin Pharmacol. 2008; 64:43-50. http://www.ncbi.nlm.nih.gov/pubmed/18040672?dopt=AbstractPlus
247. Bayer. Adempas (riociguat) tablets prescribing information. Whippany, NJ; 2021 Sep.
249. Muirhead GJ, Rance DJ, Walker DK, Wastall P. Comparative human pharmacokinetics and metabolism of single-dose oral and intravenous sildenafil. Br J Clin Pharmacol. 2002;53 Suppl 1(Suppl 1):13S-20S. doi: 10.1046/j.06-5251.2001.00028.x. PMID: 11879255; PMCID: PMC1874255
250. Hyland R, Roe EG, Jones BC, Smith DA. Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001 Mar;51(3):239-48. doi: 10.1046/j.1365-2125.2001.00318.x. PMID: 11298070; PMCID: PMC2015027.
600. McMurray JG, Feldman RA, Auerbach SM, Deriesthal H, Wilson N; Multicenter Study Group. Long-term safety and effectiveness of sildenafil citrate in men with erectile dysfunction. Ther Clin Risk Manag. 2007 Dec;3(6):975-81. PMID: 18516312; PMCID: PMC2387281
601. Karakus S, Burnett AL. The medical and surgical treatment of erectile dysfunction: a review and update. Can J Urol. 2020 Aug;27(S3):28-35. PMID: 32876000
602. Smith WB 2nd, McCaslin IR, Gokce A, Mandava SH, Trost L, Hellstrom WJ. PDE5 inhibitors: considerations for preference and long-term adherence. Int J Clin Pract. 2013 Aug;67(8):768-80. doi: 10.1111/ijcp.12074. PMID: 23869678
603. Viigimaa M, Vlachopoulos C, Lazaridis A, Doumas M. Management of erectile dysfunction in hypertension: Tips and tricks. World J Cardiol. 2014 Sep 26;6(9):908-15. doi: 10.4330/wjc.v6.i9.908. PMID: 25276292; PMCID: PMC4176800.
Frequently asked questions
- Cialis vs Viagra - What's the difference between them?
- Do you know these 11 amazing facts about Viagra?
- Is generic Viagra available in the U.S.?
More about sildenafil
- Check interactions
- Compare alternatives
- Pricing & coupons
- Reviews (495)
- Drug images
- Latest FDA alerts (13)
- Side effects
- Dosage information
- Patient tips
- During pregnancy
- Support group
- Drug class: agents for pulmonary hypertension
- Breastfeeding
Patient resources
Professional resources
- Sildenafil (Pulmonary Hypertension) monograph
- Sildenafil Injection (FDA)
- Sildenafil Oral Suspension (FDA)
- Sildenafil Tablets (FDA)