How Sildenafil Citrate Works in the Body

"Sildenafil citrate for SSRI-induced sexual side effects". "Sildenafil in the treatment of antipsychotic-induced erectile dysfunction: a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial".

• Sildenafil’s development marked a breakthrough in ED treatment.
• It has revolutionized sexual health for many men globally.
• The drug’s mechanism enhances nitric oxide effects.
• Many patients report improved confidence with sildenafil use.
• Research continues on new formulations and delivery methods.
• Public health campaigns promote safe and effective usage.
• Awareness of contraindications reduces health risks.

"Sildenafil (viagra) facilitates weaning of inhaled nitric oxide following placement of a biventricular-assist device". "Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo controlled study". "Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder". "Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF". "Comparison of efficacy of sildenafil-only, sildenafil plus topical EMLA cream, and topical EMLA-cream-only in treatment of premature ejaculation". "Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation".

Parameter	Description	Typical Value
Absorption Rate	Time to reach peak plasma concentration	30-120 minutes
Bioavailability	Percentage of dose reaching systemic circulation	40%
Half-life	Time to reduce plasma concentration by half	4 hours
Metabolism	Primary site of metabolism	Liver (CYP3A4 enzyme)
Excretion	Main routes of elimination	Feces and urine

"Efficacy of sildenafil citrate (Viagra) in men with premature ejaculation". "Sildenafil ameliorates effects of inhaled nitric oxide withdrawal".

Condition	Description	Recommended Dosage	Notes
Erectile Dysfunction (ED)	Difficulty achieving or maintaining an erection	50 mg before activity	Can be adjusted based on response
Pulmonary Arterial Hypertension	High blood pressure in lungs	20 mg three times daily	Prescribed under medical supervision
Off-label uses	Other potential uses	Varies	Use under healthcare provider guidance

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal. A service of the National Library of Medicine, National Institutes of Health. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Sildenafil is a medication used in the management and treatment of erectile dysfunction and pulmonary arterial hypertension. It is in the phosphodiesterase-5 inhibitor (PDE5-I) class of medications. This activity describes the indications, actions, adverse effects, and contraindications of sildenafil as an agent in the clinical setting. Knowledge therein is critical for appropriate healthcare team management of patients with erectile dysfunction, pulmonary arterial hypertension, and/or related conditions. Explain the mechanism of action of sildenafil in the treatment of erectile dysfunction and pulmonary arterial hypertension. Describe the clinically important drug interactions of sildenafil.

What should I know about storage and disposal of this medication?

[19] Combining sildenafil with other CYP3A4 inducers can similarly lead to reduced sildenafil levels; thus, such combinations are not recommended with chronic sildenafil dosing as performed in managing PAH. Sildenafil, at its lowest dose, is recommended when initiating therapy in patients who are on alpha-blockers due to potential systemic hypotension. Caution is also a requirement in patients taking mixed alpha/beta-blockers unless there is specific information regarding coadministration. Doses greater than 100 mg of sildenafil have resulted in no increase in efficacy but an increase in side effects. Patients on sildenafil most commonly (2%) reported headaches, flushing, dyspepsia, nasal congestion, back pain, myalgia, nausea, dizziness, and rash. Outline appropriate monitoring of sildenafil therapy in erectile dysfunction and pulmonary arterial hypertension. Summarize the role of the interprofessional healthcare team in improving care coordination and communication to improve outcomes related to sildenafil therapy. Sildenafil was the first phosphodiesterase-5 (PDE5) inhibitor approved for use, receiving US Food and Drug Administration approval for use in erectile dysfunction (ED) on March 27, 1998. [1] It also has US Food and Drug Administration (FDA) approval for the treatment of World Health Organization (WHO) Group I pulmonary hypertension (also known as pulmonary arterial hypertension [PAH]) in adults to improve exercise tolerance and delay clinical worsening. [2] Sildenafil-induced delay in clinical worsening is demonstrated when sildenafil was used canadian sildenafil citrate concomitantly with epoprostenol therapy. Clinical trials have established effectiveness for short-term use (12-16 weeks) and included patients, mainly patients with New York Heart Association (NYHA) Functional Class II-III symptoms and having idiopathic etiology or connective tissue disease (CTD). However, the addition of sildenafil to bosentan therapy did not result in any improvement in exercise capacity. Sildenafil is also occasionally used off-label for the treatment of: The molecular structure of sildenafil mimics that of cyclic guanosine monophosphate (cGMP). This similarity protects cGMP from degradation because sildenafil can bind to the catalytic site to act as a competitive inhibitor of cGMP-specific PDE5. This enzyme normally catalyzes the breakdown of vasodilatory cGMP. When PDE5 is active, cGMP is degraded, causing the vascular smooth muscle contraction, thereby limiting blood flow. [7] When PDE5 becomes inhibited, the accumulation of cGMP leads to increased cGMP-dependent protein kinase activity, which sildenafil from canada phosphorylates multiple targets in the smooth muscle cell.

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The result of smooth muscle cell target protein phosphorylation is a decrease in intracellular calcium, increased efflux of potassium, and deactivation of myosin light chain kinase, ultimately causing smooth muscle relaxation. Relaxation of vascular smooth muscle in the corpus cavernosum leads to penile erection when the cavernosal sinusoids engorge with blood to compress the subtunical veins against the tunica albuginea. In patients with vasoactive pulmonary arterial hypertension, vasodilation of the pulmonary artery leads to reduced resistance to blood flow, with subsequent reductions in mean pulmonary arterial pressure. Sildenafil is available as oral tablets of 25 mg, 50 mg, and 100 mg strength for ED. Most patients receive a prescription for 50 mg of oral sildenafil, taken as needed approximately 1 hour before sexual activity. [7] The dose can be titrated upward to a maximum of 100 mg or down to 25 mg based on individual effectiveness and tolerance. Patients are advised not to exceed a maximum dosing frequency of once daily. It can be taken 30 minutes to 4 hours before desired intercourse. The onset of action can occur within 30 minutes, while the duration of the effect can last up to 18 hours. Consider starting at a dose of 25 mg in patients with hepatic dysfunction (eg, cirrhosis), patients with creatinine clearance (CLcr) less than 30 mL/minute (severe renal impairment), and patients age 65 years and above, as the administration of sildenafil in these group patients have resulted in higher plasma levels of sildenafil. Patients taking concomitant inhibitors of CYP3A4 may benefit from initiation at the lower dosage.

Medical uses

It is in the phosphodiesterase-5 inhibitor (PDE5-I) class of medications. This activity describes the indications, actions, adverse effects, and contraindications of sildenafil as an agent in the clinical setting. Knowledge therein is critical for appropriate healthcare team management of patients with erectile dysfunction, pulmonary arterial hypertension, and/or related conditions. Explain the mechanism of action of sildenafil in the treatment of erectile dysfunction and pulmonary arterial hypertension. Describe the clinically important drug interactions of sildenafil.

Regional issues

Outline appropriate monitoring of sildenafil therapy in erectile dysfunction and pulmonary arterial hypertension. Summarize the role of the interprofessional healthcare team in improving care coordination and communication to improve outcomes related to sildenafil therapy. Sildenafil was the first phosphodiesterase-5 (PDE5) inhibitor approved for use, receiving US Food and Drug Administration approval for use in erectile dysfunction (ED) on March 27, 1998. [1] It also has US Food and Drug Administration (FDA) approval for the treatment of World Health Organization (WHO) Group I pulmonary hypertension (also known as pulmonary arterial hypertension [PAH]) in adults to improve exercise tolerance and delay clinical worsening. [2] Sildenafil-induced delay in clinical worsening is demonstrated when sildenafil was used canadian sildenafil citrate concomitantly with epoprostenol therapy.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Clinical trials have established effectiveness for short-term use (12-16 weeks) and included patients, mainly patients with New York Heart Association (NYHA) Functional Class II-III symptoms and having idiopathic etiology or connective tissue disease (CTD). However, the addition of sildenafil to bosentan therapy did not result in any improvement in exercise capacity. Sildenafil is also occasionally used off-label for the treatment of: The molecular structure of sildenafil mimics that of cyclic guanosine monophosphate (cGMP). This similarity protects cGMP from degradation because sildenafil can bind to the catalytic site to act as a competitive inhibitor of cGMP-specific PDE5. This enzyme normally catalyzes the breakdown of vasodilatory cGMP. In the treatment of PAH, sildenafil is available in 20 mg tablets, oral suspension 10 mg/mL, and injectable 10 mg/12.5 mL forms. The recommended dosage for tablet and oral suspension formularies is 5 mg or 20 mg three times daily, 4 to 6 hours apart. Injections are dosed at 2.5 mg or 10 mg three times a day, 4 to 6 hours apart, as an intravenous bolus. [11][12] Sildenafil injection is only indicated for the continued treatment of PAH when patients are currently on prescribed oral sildenafil treatment and are temporarily unable to take medicine orally. No dose adjustment is required in patients with renal impairment (including severe impairment CLcr <30 mL/min). No dose adjustment is required for mild to moderate hepatic impairment. Its use is not studied in patients with severe hepatic impairment.

What Other Drugs Interact with Sildenafil?

Sildenafil has shown associations with changes in color vision, alterations in light perception, and hazy vision. Pediatric Patients: Increased mortality with increasing sildenafil dose was observed in a clinical trial of pediatric patients with PAH.

How Supplied

When PDE5 is active, cGMP is degraded, causing the vascular smooth muscle contraction, thereby limiting blood flow. [7] When PDE5 becomes inhibited, the accumulation of cGMP leads to increased cGMP-dependent protein kinase activity, which sildenafil from canada phosphorylates multiple targets in the smooth muscle cell. The result of smooth muscle cell target protein phosphorylation is a decrease in intracellular calcium, increased efflux of potassium, and deactivation of myosin light chain kinase, ultimately causing smooth muscle relaxation. Relaxation of vascular smooth muscle in the corpus cavernosum leads to penile erection when the cavernosal sinusoids engorge with blood to compress the subtunical veins against the tunica albuginea. In patients with vasoactive pulmonary arterial hypertension, vasodilation of the pulmonary artery leads to reduced resistance to blood flow, with subsequent reductions in mean pulmonary arterial pressure.

What should I do if I miss a dose of sildenafil?

Sildenafil is available as oral tablets of 25 mg, 50 mg, and 100 mg strength for ED. Most patients receive a prescription for 50 mg of oral sildenafil, taken as needed approximately 1 hour before sexual activity. [7] The dose can be titrated upward to a maximum of 100 mg or down to 25 mg based on individual effectiveness and tolerance. Patients are advised not to exceed a maximum dosing frequency of once daily. It can be taken 30 minutes to 4 hours before desired intercourse.

Label Warnings

The onset of action can occur within 30 minutes, while the duration of the effect can last up to 18 hours. Consider starting at a dose of 25 mg in patients with hepatic dysfunction (eg, cirrhosis), patients with creatinine clearance (CLcr) less than 30 mL/minute (severe renal impairment), and patients age 65 years and above, as the administration of sildenafil in these group patients have resulted in higher plasma levels of sildenafil. Patients taking concomitant inhibitors of CYP3A4 may benefit from initiation at the lower dosage. In the treatment of PAH, sildenafil is available in 20 mg tablets, oral suspension 10 mg/mL, and injectable 10 mg/12.5 mL forms. The recommended dosage for tablet and oral suspension formularies is 5 mg or 20 mg three times daily, 4 to 6 hours apart. Deaths were first reported after approximately 1 year of use, and hence, sildenafil, particularly chronic use, is not recommended in pediatric patients with PAH. Pregnant Women: There are increased risks for stroke, heart failure, preterm delivery, and maternal and fetal death for pregnant women with untreated pulmonary arterial hypertension. Small case studies in pregnant women with PAH indicate a low risk of harm, though caution is warranted. Breastfeeding Women: There is a lack of information about the effects of sildenafil on milk production and the effects of sildenafil on breastfed infants.

Property	Description	Value	Units
Molecular Weight	The mass of one mole of sildenafil citrate	474.58	g/mol
Chemical Formula	Molecular composition	C22H30N6O4S
Solubility	Water solubility	Slightly soluble	at 25°C
pH of Solution	Typical pH when dissolved in water	3.8 - 4.2
Melting Point	The temperature at which it melts	196 - 198	°C

Sildenafil has systemic vasodilatory effects and, as such, should be prescribed with caution to patients who may be sensitive to such blood pressure changes, such as patients with left ventricular outflow obstruction and impaired autonomic control of blood pressure. [14] Caution is needed when combining sildenafil with alpha-adrenergic blocking drugs and other antihypertensive agents.

• Sildenafil is unsuitable for individuals with severe liver disease.
• Patients should avoid alcohol consumption during treatment.
• Some side effects may resolve on their own within hours.
• Persistent side effects should prompt medical consultation.
• The drug does not cure ED but manages symptoms.
• Lifestyle changes can also improve erectile function.
• Follow your healthcare provider’s instructions precisely.

The use of sildenafil can infrequently result in a prolonged erection lasting more than 4 hours, also known as priapism, which, if left untreated, may result in damage to the penile tissue. Furthermore, sildenafil use requires caution in patients with anatomical deformation of the penis and patients with conditions potentially predisposing them to priapism, such as sickle cell anemia or multiple myeloma.

LinkOut - more resources

Injections are dosed at 2.5 mg or 10 mg three times a day, 4 to 6 hours apart, as an intravenous bolus. [11][12] Sildenafil injection is only indicated for the continued treatment of PAH when patients are currently on prescribed oral sildenafil treatment and are temporarily unable to take medicine orally. No dose adjustment is required in patients with renal impairment (including severe impairment CLcr <30 mL/min). No dose adjustment is required for mild to moderate hepatic impairment. Its use is not studied in patients with severe hepatic impairment.

Marketing and sales

Pediatric Patients: Increased mortality with increasing sildenafil dose was observed in a clinical trial of pediatric patients with PAH. Deaths were first reported after approximately 1 year of use, and hence, sildenafil, particularly chronic use, is not recommended in pediatric patients with PAH. Pregnant Women: There are increased risks for stroke, heart failure, preterm delivery, and maternal and fetal death for pregnant women with untreated pulmonary arterial hypertension. Small case studies in pregnant women with PAH indicate a low risk of harm, though caution is warranted. Breastfeeding Women: There is a lack of information about the effects of sildenafil on milk production and the effects of sildenafil on breastfed infants.

Allergy warning

Sildenafil has systemic vasodilatory effects and, as such, should be prescribed with caution to patients who may be sensitive to such blood pressure changes, such as patients with left ventricular outflow obstruction and impaired autonomic control of blood pressure. [14] Caution is needed when combining sildenafil with alpha-adrenergic blocking drugs and other antihypertensive agents. The use of sildenafil can infrequently result in a prolonged erection lasting more than 4 hours, also known as priapism, which, if left untreated, may result in damage to the penile tissue. Furthermore, sildenafil use requires caution in patients with anatomical deformation of the penis and patients with conditions potentially predisposing them to priapism, such as sickle cell anemia or multiple myeloma. Therefore, patients with a previous history of NAION or with a "crowded" optic disk should be prescribed sildenafil with caution. Therefore, patients with a previous history of NAION or with a "crowded" optic disk should be prescribed sildenafil with caution. Sildenafil metabolism is catalyzed primarily by CYP3A4 and, to lovegra sildenafil a lesser extent, by CYP2C9; thus, strong inhibitors of these isoenzymes may lead to the accumulation of sildenafil with subsequent toxicity. [18][19] The coadministration of sildenafil and ritonavir increased plasma sildenafil concentration (11-fold increase in the area under the curve due to CYP3A4/2C9 inhibition.

2. Upsides

"Sildenafil citrate for SSRI-induced sexual side effects". "Sildenafil in the treatment of antipsychotic-induced erectile dysfunction: a randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover trial". "Sildenafil (viagra) facilitates weaning of inhaled nitric oxide following placement of a biventricular-assist device". "Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo controlled study". "Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder".

Are you currently using Sildenafil (Viagra, Revatio)?

"Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF". "Comparison of efficacy of sildenafil-only, sildenafil plus topical EMLA cream, and topical EMLA-cream-only in treatment of premature ejaculation". "Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation". "Efficacy of sildenafil citrate (Viagra) in men with premature ejaculation". "Sildenafil ameliorates effects of inhaled nitric oxide withdrawal".

Patient resources

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal. A service of the National Library of Medicine, National Institutes of Health. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Sildenafil is a medication used in the management and treatment of erectile dysfunction and pulmonary arterial hypertension. Accordingly, caution is necessary for patients already on ritonavir when prescribing sildenafil. The recommendation is not to exceed a dose of 25 mg of sildenafil in 48 hours if taking ritonavir. [7] Combining sildenafil with the endothelin antagonist bosentan to manage pulmonary arterial hypertension has correlated with increased serum concentrations of bosentan and reduced levels of sildenafil. [19] Combining sildenafil with other CYP3A4 inducers can similarly lead to reduced sildenafil levels; thus, such combinations are not recommended with chronic sildenafil dosing as performed in managing PAH. Sildenafil, at its lowest dose, is recommended when initiating therapy in patients who are on alpha-blockers due to potential systemic hypotension.

Why is this medication prescribed?

Sildenafil metabolism is catalyzed primarily by CYP3A4 and, to lovegra sildenafil a lesser extent, by CYP2C9; thus, strong inhibitors of these isoenzymes may lead to the accumulation of sildenafil with subsequent toxicity. [18][19] The coadministration of sildenafil and ritonavir increased plasma sildenafil concentration (11-fold increase in the area under the curve due to CYP3A4/2C9 inhibition. Accordingly, caution is necessary for patients already on ritonavir when prescribing sildenafil. The recommendation is not to exceed a dose of 25 mg of sildenafil in 48 hours if taking ritonavir. [7] Combining sildenafil with the endothelin antagonist bosentan to manage pulmonary arterial hypertension has correlated with increased serum concentrations of bosentan and reduced levels of sildenafil. Caution is also a requirement in patients taking mixed alpha/beta-blockers unless there is specific information regarding coadministration. Doses greater than 100 mg of sildenafil have resulted in no increase in efficacy but an increase in side effects. Patients on sildenafil most commonly (2%) reported headaches, flushing, dyspepsia, nasal congestion, back pain, myalgia, nausea, dizziness, and rash. Sildenafil has shown associations with changes in color vision, alterations in light perception, and hazy vision.