Sildenafil

updated

Sildenafil is an FDA-approved medicine for erectile dysfunction (VIAGRA, 1998) and pulmonary arterial hypertension (REVATIO, 2005), with large randomized trials and meta-analyses behind both uses. A PubMed search on 9 October 2026 returned 25 records on sildenafil and resistance training or weightlifting in healthy people or athletes, and none tested lifting performance or muscle pump. The altitude endurance data are mixed and apply to low-oxygen conditions.

Phosphodiesterase-5 inhibitor

  • FDA first approved sildenafil as VIAGRA on 27 March 1998 and as REVATIO for pulmonary arterial hypertension on 3 June 2005.
  • In the last 4 weeks of a 12-week flexible-dose trial in 329 men with erectile dysfunction, 69% of intercourse attempts succeeded on sildenafil versus 22% on placebo.
  • SUPER-1 (278 patients with pulmonary arterial hypertension, 12 weeks) raised placebo-corrected six-minute walk distance by 45, 46 and 50 m.
  • Altitude results are mixed: two small trials reported gains under hypoxia, and a third found none at simulated altitude.
  • The VIAGRA label contraindicates organic nitrates or nitrites and warns about priapism, sudden vision loss, sudden hearing loss and low blood pressure.
  • The label states sildenafil has no effect without sexual stimulation, so it supports erection, not desire.

What is sildenafil approved to do?

FDA approved sildenafil for erectile dysfunction as VIAGRA in 1998 and for pulmonary arterial hypertension as REVATIO in 2005.

VIAGRA is labeled for erectile dysfunction. REVATIO is labeled for pulmonary arterial hypertension (WHO Group I) in adults, to improve exercise ability and delay clinical worsening, and in patients 1 to 17 years old. The label versions used here took effect on 17 November 2023 (VIAGRA) and 18 December 2024 (REVATIO).

FDA approved VIAGRA under NDA 020895 on 27 March 1998. REVATIO followed under NDA 021845 on 3 June 2005, with later applications for other forms under NDA 022473 (18 November 2009) and NDA 203109 (30 August 2012). Approvals outside the United States are not covered here.

The active molecule is sildenafil free base (C22H30N6O4S, 474.6 g/mol, CAS 139755-83-2). The marketed salt is sildenafil citrate (C28H38N6O11S, 666.7 g/mol, CAS 171599-83-0), and label doses are expressed as sildenafil.

VIAGRA label, version effective 17 November 2023: indication, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. VIAGRA (sildenafil citrate) film-coated oral tablets, 25, 50 and 100 mg, prescribing information, label version effective 17 November 2023. Set ID d905dc8d-917f-4ea3-a4ee-a1ecf6967d4e.

The label approves VIAGRA for erectile dysfunction. It contraindicates organic nitrates or nitrites and guanylate cyclase stimulators such as riociguat, and warns about priapism, sudden vision loss that could signal NAION, sudden hearing loss, and low blood pressure with alpha-blockers or other antihypertensives. Mean absolute oral bioavailability is 41% (range 25 to 63%). Clearance is mainly hepatic through CYP3A4, with an active N-desmethyl metabolite, and both have terminal half-lives of about 4 hours. A high-fat meal delays Tmax by a mean 60 minutes and lowers Cmax by a mean 29%. At recommended doses sildenafil has no effect without sexual stimulation.

Participants / model
Men with erectile dysfunction; label PK participants
Treatment
VIAGRA film-coated oral tablets, 25, 50 and 100 mg
Follow-up
Label version effective 17 November 2023
Study design
FDA prescribing information
Funding
not stated in the source

The label supports erection, not desire. Vision and hearing events are label warnings; this page gives no incidence figure for them.

Read the original source
REVATIO label, version effective 18 December 2024: indication

FDA prescribing information

DailyMed, U.S. National Library of Medicine. REVATIO (sildenafil) oral tablets, oral suspension and intravenous injection, prescribing information, label version effective 18 December 2024. Set ID 3bb9363e-b28d-4019-8aae-539233dca214.

The label approves REVATIO for pulmonary arterial hypertension (WHO Group I) in adults, to improve exercise ability and delay clinical worsening, and in patients 1 to 17 years old.

Participants / model
Adults and children 1 to 17 years old with pulmonary arterial hypertension
Treatment
REVATIO oral tablets, oral suspension and intravenous injection
Follow-up
Label version effective 18 December 2024
Study design
FDA prescribing information
Funding
not stated in the source

This is the pulmonary arterial hypertension label. It does not address erectile dysfunction or training use.

Read the original source
Drugs@FDA: sildenafil approval dates, 1998 to 2012

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020895 (VIAGRA), with related sildenafil applications NDA 021845, NDA 022473 and NDA 203109. Dates read from the openFDA Drugs@FDA records.

FDA first approved sildenafil as VIAGRA under NDA 020895 on 27 March 1998. REVATIO followed under NDA 021845 on 3 June 2005, with later applications for other forms (NDA 022473 on 18 November 2009, NDA 203109 on 30 August 2012).

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1998 to 2012
Study design
FDA application records
Funding
not stated in the source

These records give approval dates. Indications come from the product labels.

Read the original source
PubChem: sildenafil and sildenafil citrate identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 135398744 (sildenafil) and CID 135413523 (sildenafil citrate).

Sildenafil free base: C22H30N6O4S, 474.6 g/mol, CAS 139755-83-2. Sildenafil citrate, the salt in VIAGRA and REVATIO: CID 135413523, C28H38N6O11S, 666.7 g/mol, CAS 171599-83-0. Doses on labels are expressed as sildenafil.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the erectile dysfunction trials find?

Sildenafil improved erectile function over placebo in randomized trials and in a pooled analysis. Headache, flushing and dyspepsia were the most common side effects.

Two sequential double-blind trials in men with erectile dysfunction of organic, psychogenic or mixed cause tested oral sildenafil taken as needed. One was a 24-week dose-response study in 532 men (25, 50 or 100 mg, or placebo) and the other a 12-week flexible-dose study in 329 men. In the last 4 weeks of the flexible-dose study, 69% of intercourse attempts succeeded on sildenafil versus 22% on placebo. Headache, flushing and dyspepsia were the most common side effects, in 6 to 18% of men. The endpoints in these two trials were IIEF scores, successful intercourse attempts and adverse events.

A systematic review and meta-analysis of randomized trials in men with erectile dysfunction found sildenafil improved erectile function over placebo in every subgroup evaluated.

Two ED trials: 532 men for 24 weeks, 329 men for 12 weeks

Randomized controlled trial

Goldstein I et al. N Engl J Med. 1998;338(20):1397-404. PMID 9580646.

In the last 4 weeks of the flexible-dose study, 69% of intercourse attempts succeeded on sildenafil versus 22% on placebo. Headache, flushing and dyspepsia were the most common side effects, in 6 to 18% of men.

Participants / model
Men with erectile dysfunction of organic, psychogenic or mixed cause; 532 in the dose-response study and 329 in the flexible-dose study
Treatment
Oral sildenafil as needed: 25, 50 or 100 mg or placebo in the dose-response study; flexible dosing in the flexible-dose study
Follow-up
24 weeks (dose-response study) and 12 weeks (flexible-dose study)
Study design
Two sequential double-blind randomized trials
Funding
not stated in the source

Endpoints were IIEF scores, successful intercourse attempts and adverse events in men with erectile dysfunction.

Read the original source
ED meta-analysis: improvement over placebo in every subgroup

Systematic review and meta-analysis

Fink HA et al. Arch Intern Med. 2002;162(12):1349-60. PMID 12076233.

Sildenafil improved erectile function over placebo in every subgroup evaluated. Flushing (12%), headache (11%), dyspepsia (5%) and visual disturbances (3%) were the specific side effects. Sildenafil was not significantly associated with serious cardiovascular events or death in the pooled trials.

Participants / model
Men with erectile dysfunction across pooled randomized trials
Treatment
Oral sildenafil
Follow-up
Pooled randomized trials
Study design
Systematic review and meta-analysis
Funding
not stated in the source

The serious-event findings apply to the pooled randomized trials, not to every user.

Read the original source

What did SUPER-1 show in pulmonary arterial hypertension?

In 278 patients with symptomatic pulmonary arterial hypertension, 12 weeks of sildenafil raised placebo-corrected six-minute walk distance by 45 to 50 m. Clinical worsening did not differ from placebo.

SUPER-1 randomized 278 patients with symptomatic PAH (idiopathic PAH, PAH with connective-tissue disease, or repaired congenital shunts) to placebo or sildenafil 20, 40 or 80 mg three times a day for 12 weeks. Placebo-corrected six-minute walk distance rose 45, 46 and 50 m across the three doses. All doses lowered mean pulmonary artery pressure and improved WHO functional class.

The population was patients with pulmonary arterial hypertension, so the walk-distance result does not apply to healthy people.

SUPER-1: 278 patients, 12 weeks, walk distance up 45 to 50 m

Randomized controlled trial

Galiè N et al. N Engl J Med. 2005;353(20):2148-57. PMID 16291984.

Placebo-corrected six-minute walk distance rose 45, 46 and 50 m. All doses lowered mean pulmonary artery pressure and improved WHO functional class. Clinical worsening did not differ from placebo.

Participants / model
278 patients with symptomatic PAH: idiopathic PAH, PAH with connective-tissue disease, or repaired congenital shunts
Treatment
Oral sildenafil 20, 40 or 80 mg three times a day, or placebo
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Pulmonary arterial hypertension population; the walk-distance result does not apply to healthy people.

Read the original source
REVATIO label, version effective 18 December 2024: indication

FDA prescribing information

DailyMed, U.S. National Library of Medicine. REVATIO (sildenafil) oral tablets, oral suspension and intravenous injection, prescribing information, label version effective 18 December 2024. Set ID 3bb9363e-b28d-4019-8aae-539233dca214.

The label approves REVATIO for pulmonary arterial hypertension (WHO Group I) in adults, to improve exercise ability and delay clinical worsening, and in patients 1 to 17 years old.

Participants / model
Adults and children 1 to 17 years old with pulmonary arterial hypertension
Treatment
REVATIO oral tablets, oral suspension and intravenous injection
Follow-up
Label version effective 18 December 2024
Study design
FDA prescribing information
Funding
not stated in the source

This is the pulmonary arterial hypertension label. It does not address erectile dysfunction or training use.

Read the original source

Does sildenafil add pump, vascularity or lifting performance in training?

No trial found tests it. A PubMed search on 9 October 2026 returned 25 records on sildenafil with resistance exercise, resistance training, strength training or weightlifting in healthy people or athletes; none tested lifting performance or muscle pump in healthy people.

Sellers market off-label sildenafil for muscle pump and vascularity during training, and for erectile and libido support. The 25 records covered pulmonary hypertension, altitude endurance and disease populations. The training pump use has no trial behind it among those records.

The erectile claim is the labeled use, covered above. On libido, the VIAGRA label states that at recommended doses sildenafil has no effect without sexual stimulation, so it supports erection, not desire.

PubMed search, 9 October 2026: 25 records, none on lifting or pump

PubMed search record

PubMed search run on 9 October 2026: sildenafil AND (resistance exercise OR resistance training OR strength training OR weightlifting) AND (healthy OR athletes). 25 records returned.

The search returned 25 records. None tested lifting performance or muscle pump in healthy people; they covered pulmonary hypertension, altitude endurance and disease populations. The training pump use has no trial behind it among these records.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
VIAGRA label, version effective 17 November 2023: indication, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. VIAGRA (sildenafil citrate) film-coated oral tablets, 25, 50 and 100 mg, prescribing information, label version effective 17 November 2023. Set ID d905dc8d-917f-4ea3-a4ee-a1ecf6967d4e.

The label approves VIAGRA for erectile dysfunction. It contraindicates organic nitrates or nitrites and guanylate cyclase stimulators such as riociguat, and warns about priapism, sudden vision loss that could signal NAION, sudden hearing loss, and low blood pressure with alpha-blockers or other antihypertensives. Mean absolute oral bioavailability is 41% (range 25 to 63%). Clearance is mainly hepatic through CYP3A4, with an active N-desmethyl metabolite, and both have terminal half-lives of about 4 hours. A high-fat meal delays Tmax by a mean 60 minutes and lowers Cmax by a mean 29%. At recommended doses sildenafil has no effect without sexual stimulation.

Participants / model
Men with erectile dysfunction; label PK participants
Treatment
VIAGRA film-coated oral tablets, 25, 50 and 100 mg
Follow-up
Label version effective 17 November 2023
Study design
FDA prescribing information
Funding
not stated in the source

The label supports erection, not desire. Vision and hearing events are label warnings; this page gives no incidence figure for them.

Read the original source

Do the altitude studies support a performance effect?

The results are mixed. Gains appeared only under low oxygen and not in every study, and none tested strength.

In a randomized double-blind crossover trial in 14 healthy participants, 50 mg sildenafil raised maximum workload under acute hypoxia at low altitude (172.5 W versus 130.6 W on placebo). It also raised workload and lowered pulmonary artery pressure at Mount Everest base camp. This is hypoxia evidence, not sea-level or strength evidence.

In 10 trained men given placebo, 50 mg or 100 mg 1 hour before cycling, sildenafil improved cardiac output and time-trial performance in acute hypoxia but not in normoxia. The gains concentrated in a post hoc responder subgroup.

In 11 men and 10 women at simulated moderate (about 2,100 m) and high (about 3,900 m) altitude, 50 mg sildenafil did not improve steady-state hemodynamics, peak power or a 15-km cycling time trial. The altitude benefit is not consistent across studies.

Hypoxia crossover: 14 healthy participants, 50 mg

Randomized controlled trial

Ghofrani HA et al. Ann Intern Med. 2004;141(3):169-77. PMID 15289213.

Sildenafil 50 mg raised maximum workload under acute hypoxia at low altitude (172.5 W versus 130.6 W on placebo). It also raised workload and lowered pulmonary artery pressure at Mount Everest base camp.

Participants / model
14 healthy participants
Treatment
Oral sildenafil 50 mg or placebo
Follow-up
Acute hypoxia at low altitude and at Mount Everest base camp
Study design
Randomized double-blind crossover trial
Funding
not stated in the source

This is hypoxia evidence, not sea-level or strength evidence.

Read the original source
Trained men: 10 men, gains in hypoxia only

Randomized controlled trial

Hsu AR et al. J Appl Physiol (1985). 2006;100(6):2031-40. PMID 16455814.

Sildenafil improved cardiac output and time-trial performance in acute hypoxia but not in normoxia. Gains concentrated in a post hoc responder subgroup.

Participants / model
10 trained men
Treatment
Oral sildenafil 50 or 100 mg, or placebo, 1 hour before cycling
Follow-up
not stated in the source
Study design
Randomized trial with placebo, 50 mg and 100 mg conditions
Funding
not stated in the source

The gains came from a post hoc responder subgroup and did not appear in normoxia.

Read the original source
Simulated altitude: 11 men and 10 women, no performance gain

Randomized controlled trial

Kressler J et al. Eur J Appl Physiol. 2011;111(12):3031-40. PMID 21451938.

Sildenafil 50 mg did not improve steady-state hemodynamics, peak power or 15-km cycling time trial at simulated moderate (about 2,100 m) and high (about 3,900 m) altitude.

Participants / model
11 men and 10 women
Treatment
Oral sildenafil 50 mg
Follow-up
Simulated moderate (about 2,100 m) and high (about 3,900 m) altitude
Study design
Randomized trial
Funding
not stated in the source

The altitude benefit is not consistent across studies.

Read the original source

How does sildenafil work, and what does the body do with it?

Sildenafil is a phosphodiesterase-5 inhibitor. At recommended doses the label says it has no effect without sexual stimulation, and its terminal half-life is about 4 hours.

The VIAGRA label states that at recommended doses sildenafil has no effect without sexual stimulation, so it supports erection, not desire. Class membership and label pharmacology do not show an effect on lifting performance. That needs its own trial, and the PubMed search above found none.

Mean absolute oral bioavailability is 41% (range 25 to 63%). Clearance is mainly hepatic through CYP3A4, with an active N-desmethyl metabolite, and both sildenafil and the metabolite have terminal half-lives of about 4 hours. A high-fat meal delays Tmax by a mean 60 minutes and lowers Cmax by a mean 29%.

VIAGRA label, version effective 17 November 2023: indication, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. VIAGRA (sildenafil citrate) film-coated oral tablets, 25, 50 and 100 mg, prescribing information, label version effective 17 November 2023. Set ID d905dc8d-917f-4ea3-a4ee-a1ecf6967d4e.

The label approves VIAGRA for erectile dysfunction. It contraindicates organic nitrates or nitrites and guanylate cyclase stimulators such as riociguat, and warns about priapism, sudden vision loss that could signal NAION, sudden hearing loss, and low blood pressure with alpha-blockers or other antihypertensives. Mean absolute oral bioavailability is 41% (range 25 to 63%). Clearance is mainly hepatic through CYP3A4, with an active N-desmethyl metabolite, and both have terminal half-lives of about 4 hours. A high-fat meal delays Tmax by a mean 60 minutes and lowers Cmax by a mean 29%. At recommended doses sildenafil has no effect without sexual stimulation.

Participants / model
Men with erectile dysfunction; label PK participants
Treatment
VIAGRA film-coated oral tablets, 25, 50 and 100 mg
Follow-up
Label version effective 17 November 2023
Study design
FDA prescribing information
Funding
not stated in the source

The label supports erection, not desire. Vision and hearing events are label warnings; this page gives no incidence figure for them.

Read the original source

What risks do the label and trials report?

The label warns about priapism, sudden vision loss, sudden hearing loss and low blood pressure, and contraindicates organic nitrates or nitrites and guanylate cyclase stimulators such as riociguat.

The VIAGRA label contraindicates organic nitrates or nitrites and guanylate cyclase stimulators such as riociguat. Its warnings cover priapism, sudden vision loss that could signal NAION, sudden hearing loss, and low blood pressure with alpha-blockers or other antihypertensives. Incidence figures for the vision and hearing events are not given here.

In the two sequential trials, headache, flushing and dyspepsia were the most common side effects, in 6 to 18% of men. A meta-analysis reported flushing in 12%, headache in 11%, dyspepsia in 5% and visual disturbances in 3%, and found sildenafil was not significantly associated with serious cardiovascular events or death in the pooled trials.

A harms meta-analysis of 49 randomized trials found more all-cause adverse events with sildenafil (RR 1.56, 95% CI 1.38 to 1.76), with no difference in serious adverse events or adverse-event withdrawals. It also found a lack of trials reporting harms beyond 6 months.

VIAGRA label, version effective 17 November 2023: indication, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. VIAGRA (sildenafil citrate) film-coated oral tablets, 25, 50 and 100 mg, prescribing information, label version effective 17 November 2023. Set ID d905dc8d-917f-4ea3-a4ee-a1ecf6967d4e.

The label approves VIAGRA for erectile dysfunction. It contraindicates organic nitrates or nitrites and guanylate cyclase stimulators such as riociguat, and warns about priapism, sudden vision loss that could signal NAION, sudden hearing loss, and low blood pressure with alpha-blockers or other antihypertensives. Mean absolute oral bioavailability is 41% (range 25 to 63%). Clearance is mainly hepatic through CYP3A4, with an active N-desmethyl metabolite, and both have terminal half-lives of about 4 hours. A high-fat meal delays Tmax by a mean 60 minutes and lowers Cmax by a mean 29%. At recommended doses sildenafil has no effect without sexual stimulation.

Participants / model
Men with erectile dysfunction; label PK participants
Treatment
VIAGRA film-coated oral tablets, 25, 50 and 100 mg
Follow-up
Label version effective 17 November 2023
Study design
FDA prescribing information
Funding
not stated in the source

The label supports erection, not desire. Vision and hearing events are label warnings; this page gives no incidence figure for them.

Read the original source
Two ED trials: 532 men for 24 weeks, 329 men for 12 weeks

Randomized controlled trial

Goldstein I et al. N Engl J Med. 1998;338(20):1397-404. PMID 9580646.

In the last 4 weeks of the flexible-dose study, 69% of intercourse attempts succeeded on sildenafil versus 22% on placebo. Headache, flushing and dyspepsia were the most common side effects, in 6 to 18% of men.

Participants / model
Men with erectile dysfunction of organic, psychogenic or mixed cause; 532 in the dose-response study and 329 in the flexible-dose study
Treatment
Oral sildenafil as needed: 25, 50 or 100 mg or placebo in the dose-response study; flexible dosing in the flexible-dose study
Follow-up
24 weeks (dose-response study) and 12 weeks (flexible-dose study)
Study design
Two sequential double-blind randomized trials
Funding
not stated in the source

Endpoints were IIEF scores, successful intercourse attempts and adverse events in men with erectile dysfunction.

Read the original source
ED meta-analysis: improvement over placebo in every subgroup

Systematic review and meta-analysis

Fink HA et al. Arch Intern Med. 2002;162(12):1349-60. PMID 12076233.

Sildenafil improved erectile function over placebo in every subgroup evaluated. Flushing (12%), headache (11%), dyspepsia (5%) and visual disturbances (3%) were the specific side effects. Sildenafil was not significantly associated with serious cardiovascular events or death in the pooled trials.

Participants / model
Men with erectile dysfunction across pooled randomized trials
Treatment
Oral sildenafil
Follow-up
Pooled randomized trials
Study design
Systematic review and meta-analysis
Funding
not stated in the source

The serious-event findings apply to the pooled randomized trials, not to every user.

Read the original source
Harms meta-analysis: 49 trials, RR 1.56 for all-cause adverse events

Systematic review and meta-analysis

Tsertsvadze A et al. Urology. 2009;74(4):831-836.e8. PMID 19592078.

More all-cause adverse events occurred with sildenafil (RR 1.56, 95% CI 1.38 to 1.76), with no difference in serious adverse events or adverse-event withdrawals. The authors also found a lack of trials reporting harms beyond 6 months.

Participants / model
Men with erectile dysfunction in short-term randomized trials
Treatment
Oral sildenafil
Follow-up
Short-term trials; harms beyond 6 months were not reported
Study design
Systematic review and meta-analysis of harms, 49 randomized trials
Funding
not stated in the source

Applies to short-term trials in men with erectile dysfunction.

Read the original source

What happened when sildenafil was tested in pregnancy?

The Dutch STRIDER trial was halted in July 2018. Sildenafil did not reduce perinatal death or major neonatal morbidity, and neonatal pulmonary hypertension was more common.

STRIDER randomized 216 pregnant women with severe early-onset fetal growth restriction. Sildenafil did not reduce perinatal death or major neonatal morbidity (60.2% versus 54.2%, RR 1.11, 95% CI 0.88 to 1.40), and neonatal pulmonary hypertension was more common (18.8% versus 5.1%, RR 3.67, 95% CI 1.28 to 10.51). The trial is registered as NCT02277132.

Fetal growth restriction is not a labeled use. The result applies to that population and to newborns exposed through maternal sildenafil, not to men taking it for erectile dysfunction.

STRIDER (Dutch): 216 pregnant women, halted July 2018

Randomized controlled trial

Pels A et al. JAMA Netw Open. 2020;3(6):e205323. PMID 32585017.

Sildenafil did not reduce perinatal death or major neonatal morbidity (60.2% versus 54.2%, RR 1.11, 95% CI 0.88 to 1.40). Neonatal pulmonary hypertension was more common (18.8% versus 5.1%, RR 3.67, 95% CI 1.28 to 10.51).

Participants / model
216 pregnant women with severe early-onset fetal growth restriction, and their newborns
Treatment
Maternal oral sildenafil
Follow-up
Halted in July 2018
Study design
Randomized trial, halted July 2018
Funding
not stated in the source

A non-labeled use in pregnancy; the result does not apply to men taking sildenafil for erectile dysfunction.

Read the original source

Why does sildenafil sit in S tier?

Two FDA approvals, large randomized trials and meta-analyses, and nearly three decades of use for erectile dysfunction support the S for the approved uses. The grade does not cover the supplier's training claim.

The S applies to erectile dysfunction and pulmonary arterial hypertension. The supplier's training claim is a separate question: the altitude data are mixed and apply to low-oxygen conditions, and nothing found in the PubMed search tests strength or pump.

The pregnancy trial adds a population in which sildenafil did not improve outcomes and neonatal pulmonary hypertension was more common.

VIAGRA label, version effective 17 November 2023: indication, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. VIAGRA (sildenafil citrate) film-coated oral tablets, 25, 50 and 100 mg, prescribing information, label version effective 17 November 2023. Set ID d905dc8d-917f-4ea3-a4ee-a1ecf6967d4e.

The label approves VIAGRA for erectile dysfunction. It contraindicates organic nitrates or nitrites and guanylate cyclase stimulators such as riociguat, and warns about priapism, sudden vision loss that could signal NAION, sudden hearing loss, and low blood pressure with alpha-blockers or other antihypertensives. Mean absolute oral bioavailability is 41% (range 25 to 63%). Clearance is mainly hepatic through CYP3A4, with an active N-desmethyl metabolite, and both have terminal half-lives of about 4 hours. A high-fat meal delays Tmax by a mean 60 minutes and lowers Cmax by a mean 29%. At recommended doses sildenafil has no effect without sexual stimulation.

Participants / model
Men with erectile dysfunction; label PK participants
Treatment
VIAGRA film-coated oral tablets, 25, 50 and 100 mg
Follow-up
Label version effective 17 November 2023
Study design
FDA prescribing information
Funding
not stated in the source

The label supports erection, not desire. Vision and hearing events are label warnings; this page gives no incidence figure for them.

Read the original source
REVATIO label, version effective 18 December 2024: indication

FDA prescribing information

DailyMed, U.S. National Library of Medicine. REVATIO (sildenafil) oral tablets, oral suspension and intravenous injection, prescribing information, label version effective 18 December 2024. Set ID 3bb9363e-b28d-4019-8aae-539233dca214.

The label approves REVATIO for pulmonary arterial hypertension (WHO Group I) in adults, to improve exercise ability and delay clinical worsening, and in patients 1 to 17 years old.

Participants / model
Adults and children 1 to 17 years old with pulmonary arterial hypertension
Treatment
REVATIO oral tablets, oral suspension and intravenous injection
Follow-up
Label version effective 18 December 2024
Study design
FDA prescribing information
Funding
not stated in the source

This is the pulmonary arterial hypertension label. It does not address erectile dysfunction or training use.

Read the original source
Two ED trials: 532 men for 24 weeks, 329 men for 12 weeks

Randomized controlled trial

Goldstein I et al. N Engl J Med. 1998;338(20):1397-404. PMID 9580646.

In the last 4 weeks of the flexible-dose study, 69% of intercourse attempts succeeded on sildenafil versus 22% on placebo. Headache, flushing and dyspepsia were the most common side effects, in 6 to 18% of men.

Participants / model
Men with erectile dysfunction of organic, psychogenic or mixed cause; 532 in the dose-response study and 329 in the flexible-dose study
Treatment
Oral sildenafil as needed: 25, 50 or 100 mg or placebo in the dose-response study; flexible dosing in the flexible-dose study
Follow-up
24 weeks (dose-response study) and 12 weeks (flexible-dose study)
Study design
Two sequential double-blind randomized trials
Funding
not stated in the source

Endpoints were IIEF scores, successful intercourse attempts and adverse events in men with erectile dysfunction.

Read the original source
ED meta-analysis: improvement over placebo in every subgroup

Systematic review and meta-analysis

Fink HA et al. Arch Intern Med. 2002;162(12):1349-60. PMID 12076233.

Sildenafil improved erectile function over placebo in every subgroup evaluated. Flushing (12%), headache (11%), dyspepsia (5%) and visual disturbances (3%) were the specific side effects. Sildenafil was not significantly associated with serious cardiovascular events or death in the pooled trials.

Participants / model
Men with erectile dysfunction across pooled randomized trials
Treatment
Oral sildenafil
Follow-up
Pooled randomized trials
Study design
Systematic review and meta-analysis
Funding
not stated in the source

The serious-event findings apply to the pooled randomized trials, not to every user.

Read the original source
SUPER-1: 278 patients, 12 weeks, walk distance up 45 to 50 m

Randomized controlled trial

Galiè N et al. N Engl J Med. 2005;353(20):2148-57. PMID 16291984.

Placebo-corrected six-minute walk distance rose 45, 46 and 50 m. All doses lowered mean pulmonary artery pressure and improved WHO functional class. Clinical worsening did not differ from placebo.

Participants / model
278 patients with symptomatic PAH: idiopathic PAH, PAH with connective-tissue disease, or repaired congenital shunts
Treatment
Oral sildenafil 20, 40 or 80 mg three times a day, or placebo
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Pulmonary arterial hypertension population; the walk-distance result does not apply to healthy people.

Read the original source
PubMed search, 9 October 2026: 25 records, none on lifting or pump

PubMed search record

PubMed search run on 9 October 2026: sildenafil AND (resistance exercise OR resistance training OR strength training OR weightlifting) AND (healthy OR athletes). 25 records returned.

The search returned 25 records. None tested lifting performance or muscle pump in healthy people; they covered pulmonary hypertension, altitude endurance and disease populations. The training pump use has no trial behind it among these records.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

VIAGRA label, version effective 17 November 2023: indication, PK, warnings

FDA prescribing information

DailyMed, U.S. National Library of Medicine. VIAGRA (sildenafil citrate) film-coated oral tablets, 25, 50 and 100 mg, prescribing information, label version effective 17 November 2023. Set ID d905dc8d-917f-4ea3-a4ee-a1ecf6967d4e.

The label approves VIAGRA for erectile dysfunction. It contraindicates organic nitrates or nitrites and guanylate cyclase stimulators such as riociguat, and warns about priapism, sudden vision loss that could signal NAION, sudden hearing loss, and low blood pressure with alpha-blockers or other antihypertensives. Mean absolute oral bioavailability is 41% (range 25 to 63%). Clearance is mainly hepatic through CYP3A4, with an active N-desmethyl metabolite, and both have terminal half-lives of about 4 hours. A high-fat meal delays Tmax by a mean 60 minutes and lowers Cmax by a mean 29%. At recommended doses sildenafil has no effect without sexual stimulation.

Participants / model
Men with erectile dysfunction; label PK participants
Treatment
VIAGRA film-coated oral tablets, 25, 50 and 100 mg
Follow-up
Label version effective 17 November 2023
Study design
FDA prescribing information
Funding
not stated in the source

The label supports erection, not desire. Vision and hearing events are label warnings; this page gives no incidence figure for them.

Read the original source
REVATIO label, version effective 18 December 2024: indication

FDA prescribing information

DailyMed, U.S. National Library of Medicine. REVATIO (sildenafil) oral tablets, oral suspension and intravenous injection, prescribing information, label version effective 18 December 2024. Set ID 3bb9363e-b28d-4019-8aae-539233dca214.

The label approves REVATIO for pulmonary arterial hypertension (WHO Group I) in adults, to improve exercise ability and delay clinical worsening, and in patients 1 to 17 years old.

Participants / model
Adults and children 1 to 17 years old with pulmonary arterial hypertension
Treatment
REVATIO oral tablets, oral suspension and intravenous injection
Follow-up
Label version effective 18 December 2024
Study design
FDA prescribing information
Funding
not stated in the source

This is the pulmonary arterial hypertension label. It does not address erectile dysfunction or training use.

Read the original source
Drugs@FDA: sildenafil approval dates, 1998 to 2012

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 020895 (VIAGRA), with related sildenafil applications NDA 021845, NDA 022473 and NDA 203109. Dates read from the openFDA Drugs@FDA records.

FDA first approved sildenafil as VIAGRA under NDA 020895 on 27 March 1998. REVATIO followed under NDA 021845 on 3 June 2005, with later applications for other forms (NDA 022473 on 18 November 2009, NDA 203109 on 30 August 2012).

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1998 to 2012
Study design
FDA application records
Funding
not stated in the source

These records give approval dates. Indications come from the product labels.

Read the original source
Two ED trials: 532 men for 24 weeks, 329 men for 12 weeks

Randomized controlled trial

Goldstein I et al. N Engl J Med. 1998;338(20):1397-404. PMID 9580646.

In the last 4 weeks of the flexible-dose study, 69% of intercourse attempts succeeded on sildenafil versus 22% on placebo. Headache, flushing and dyspepsia were the most common side effects, in 6 to 18% of men.

Participants / model
Men with erectile dysfunction of organic, psychogenic or mixed cause; 532 in the dose-response study and 329 in the flexible-dose study
Treatment
Oral sildenafil as needed: 25, 50 or 100 mg or placebo in the dose-response study; flexible dosing in the flexible-dose study
Follow-up
24 weeks (dose-response study) and 12 weeks (flexible-dose study)
Study design
Two sequential double-blind randomized trials
Funding
not stated in the source

Endpoints were IIEF scores, successful intercourse attempts and adverse events in men with erectile dysfunction.

Read the original source
ED meta-analysis: improvement over placebo in every subgroup

Systematic review and meta-analysis

Fink HA et al. Arch Intern Med. 2002;162(12):1349-60. PMID 12076233.

Sildenafil improved erectile function over placebo in every subgroup evaluated. Flushing (12%), headache (11%), dyspepsia (5%) and visual disturbances (3%) were the specific side effects. Sildenafil was not significantly associated with serious cardiovascular events or death in the pooled trials.

Participants / model
Men with erectile dysfunction across pooled randomized trials
Treatment
Oral sildenafil
Follow-up
Pooled randomized trials
Study design
Systematic review and meta-analysis
Funding
not stated in the source

The serious-event findings apply to the pooled randomized trials, not to every user.

Read the original source
Harms meta-analysis: 49 trials, RR 1.56 for all-cause adverse events

Systematic review and meta-analysis

Tsertsvadze A et al. Urology. 2009;74(4):831-836.e8. PMID 19592078.

More all-cause adverse events occurred with sildenafil (RR 1.56, 95% CI 1.38 to 1.76), with no difference in serious adverse events or adverse-event withdrawals. The authors also found a lack of trials reporting harms beyond 6 months.

Participants / model
Men with erectile dysfunction in short-term randomized trials
Treatment
Oral sildenafil
Follow-up
Short-term trials; harms beyond 6 months were not reported
Study design
Systematic review and meta-analysis of harms, 49 randomized trials
Funding
not stated in the source

Applies to short-term trials in men with erectile dysfunction.

Read the original source
SUPER-1: 278 patients, 12 weeks, walk distance up 45 to 50 m

Randomized controlled trial

Galiè N et al. N Engl J Med. 2005;353(20):2148-57. PMID 16291984.

Placebo-corrected six-minute walk distance rose 45, 46 and 50 m. All doses lowered mean pulmonary artery pressure and improved WHO functional class. Clinical worsening did not differ from placebo.

Participants / model
278 patients with symptomatic PAH: idiopathic PAH, PAH with connective-tissue disease, or repaired congenital shunts
Treatment
Oral sildenafil 20, 40 or 80 mg three times a day, or placebo
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

Pulmonary arterial hypertension population; the walk-distance result does not apply to healthy people.

Read the original source
Hypoxia crossover: 14 healthy participants, 50 mg

Randomized controlled trial

Ghofrani HA et al. Ann Intern Med. 2004;141(3):169-77. PMID 15289213.

Sildenafil 50 mg raised maximum workload under acute hypoxia at low altitude (172.5 W versus 130.6 W on placebo). It also raised workload and lowered pulmonary artery pressure at Mount Everest base camp.

Participants / model
14 healthy participants
Treatment
Oral sildenafil 50 mg or placebo
Follow-up
Acute hypoxia at low altitude and at Mount Everest base camp
Study design
Randomized double-blind crossover trial
Funding
not stated in the source

This is hypoxia evidence, not sea-level or strength evidence.

Read the original source
Trained men: 10 men, gains in hypoxia only

Randomized controlled trial

Hsu AR et al. J Appl Physiol (1985). 2006;100(6):2031-40. PMID 16455814.

Sildenafil improved cardiac output and time-trial performance in acute hypoxia but not in normoxia. Gains concentrated in a post hoc responder subgroup.

Participants / model
10 trained men
Treatment
Oral sildenafil 50 or 100 mg, or placebo, 1 hour before cycling
Follow-up
not stated in the source
Study design
Randomized trial with placebo, 50 mg and 100 mg conditions
Funding
not stated in the source

The gains came from a post hoc responder subgroup and did not appear in normoxia.

Read the original source
Simulated altitude: 11 men and 10 women, no performance gain

Randomized controlled trial

Kressler J et al. Eur J Appl Physiol. 2011;111(12):3031-40. PMID 21451938.

Sildenafil 50 mg did not improve steady-state hemodynamics, peak power or 15-km cycling time trial at simulated moderate (about 2,100 m) and high (about 3,900 m) altitude.

Participants / model
11 men and 10 women
Treatment
Oral sildenafil 50 mg
Follow-up
Simulated moderate (about 2,100 m) and high (about 3,900 m) altitude
Study design
Randomized trial
Funding
not stated in the source

The altitude benefit is not consistent across studies.

Read the original source
STRIDER (Dutch): 216 pregnant women, halted July 2018

Randomized controlled trial

Pels A et al. JAMA Netw Open. 2020;3(6):e205323. PMID 32585017.

Sildenafil did not reduce perinatal death or major neonatal morbidity (60.2% versus 54.2%, RR 1.11, 95% CI 0.88 to 1.40). Neonatal pulmonary hypertension was more common (18.8% versus 5.1%, RR 3.67, 95% CI 1.28 to 10.51).

Participants / model
216 pregnant women with severe early-onset fetal growth restriction, and their newborns
Treatment
Maternal oral sildenafil
Follow-up
Halted in July 2018
Study design
Randomized trial, halted July 2018
Funding
not stated in the source

A non-labeled use in pregnancy; the result does not apply to men taking sildenafil for erectile dysfunction.

Read the original source
PubChem: sildenafil and sildenafil citrate identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 135398744 (sildenafil) and CID 135413523 (sildenafil citrate).

Sildenafil free base: C22H30N6O4S, 474.6 g/mol, CAS 139755-83-2. Sildenafil citrate, the salt in VIAGRA and REVATIO: CID 135413523, C28H38N6O11S, 666.7 g/mol, CAS 171599-83-0. Doses on labels are expressed as sildenafil.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

Why is Sildenafil in S tier?

S fits an approved medicine with two FDA approvals, large randomized trials and meta-analyses, and nearly three decades of use for erectile dysfunction. The grade covers the approved uses, not the supplier's training claim. The altitude data are mixed and limited to low-oxygen conditions, and nothing found tests strength or pump.