[67] No pharmacokinetic interaction has been observed between warfarin, a CYP2C9 substrate, and sildenafil. Sildenafil is a selective inhibitor of phosphodiesterases (PDEs), with the greatest selectivity for PDE type 5, the principal isoenzyme of PDE involved in the metabolism of cyclic guanosine monophosphate (cGMP) to GMP in the corpora cavernosa of the penis.

Metrics & Citations

[1][2][4][5][7][8][10][24][27][33][41][42][54][56][57][67][87][88][91][131] Sildenafil has 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] During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpora cavernosa.

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[1][2][4][56][67][91][131] By selectively inhibiting PDE type 5, sildenafil causes accumulation of cGMP in various tissues. [1][2][4][5][31][33][34][41][42][56][57][67][91][131] Because sildenafil potentiates the accumulation of cGMP rather than stimulating its production, the drug is effective only when cGMP production in the penis is increased by sexual arousal.

Why is this medication prescribed?

[34][91][131] Sildenafil at recommended doses has no effect on erectile function in the absence of sexual stimulation. [1][4][33][34][91][127][130][131][132] Sildenafil also exhibits some activity against other PDE isoenzymes. [1][4][5][31][44][57][67][87][88] In vitro, sildenafil is about 10 times more active against PDE type 5 than against PDE type 6, greater than 70-80 times more active against PDE type 5 than against PDE type 1, greater than 1000 times more active against PDE type 5 than against PDE types 2 and 4, and 4000 times more active against PDE type 5 than against PDE type 3.

• Potential side effects of sildenafil tablets include headache, flushing, and nasal congestion.
• Serious side effects are rare but can include vision changes or prolonged erections.
• Seek medical attention if you experience chest pain or an erection lasting over 4 hours.

[1][4][27][31][45][52][55][57][67][87][88] The duration of erectile responsiveness (i.e., the time period in which adequate sexual stimulation can produce an erection) with oral sildenafil has been reported to be approximately 2 hours, with some penile responsiveness persisting for up to 4 hours after oral administration. [1] In the largest clinical study published to date, the onset and duration of action of oral sildenafil were not reported. [33][34] In most other placebo-controlled studies in which improvement in erection was determined by penile plethysmography, the erectile effect was determined at a fixed time of 60 minutes after an oral dose of the drug. Sildenafil is rapidly absorbed following oral administration; the mean absolute bioavailability is 41% (range, 25-63%).

Advice To Patients

[1][4][56][67][91][116][249] Although studies indicate that more than 90% of an oral sildenafil dose is absorbed from the GI tract, the drug undergoes extensive metabolism in the GI mucosa during absorption and on first pass through the liver, with only about 40% of a dose reaching systemic circulation unchanged. [1][4][56][67][91][116][131][249] Pharmacokinetics of the drug (as determined by peak plasma concentrations or AUC) are dose proportional over the single-dose range of 1.25-200 mg.[1][4][56][91][116][131] Peak plasma concentrations of sildenafil and its active N-desmethyl metabolite are achieved within 30-120 (median: 60) minutes following oral administration in fasting adults. [1][4][91][127][130][249] Administration with a high-fat meal delays GI absorption, with a reduction in peak plasma concentrations of about 29% and a delay in time to peak plasma concentrations of about 60 minutes; the extent of absorption is not affected. Sildenafil appears to be widely distributed in the body. [1][4][67][116][131] Sildenafil and its major circulating N-desmethyl metabolite are each approximately 96% bound to plasma proteins; protein binding reportedly is independent of plasma concentration. [1][67][91][116][131] Sildenafil is distributed to a limited extent in semen following oral administration, with less than 0.001% of a single dose appearing in semen 90 minutes after dosing in healthy individuals. [1][67] Such concentrations are unlikely to cause any effects in sexual partners exposed to the semen.

• Sildenafil tablets are used to treat erectile dysfunction by improving blood flow to the penis.
• Common dosages of sildenafil tablets include 25mg, 50mg, and 100mg.
• Always follow a healthcare provider’s instructions when taking sildenafil tablets.

[67] Plasma sildenafil concentrations appear to decline in a biphasic manner following oral administration, with a terminal elimination half-life of about 4 hours (range: 3-5 hours). [1][4][67][91][116][127][130][131] Sildenafil is metabolized principally via hepatic cytochrome P-450 (CYP) microsomal isoenzymes 3A4 (major route) and 2C9 (minor route). [1][26][67][91][131] Plasma concentrations of the active N-desmethyl metabolite are approximately 40% of those observed with sildenafil, and the metabolite reportedly accounts for about 20% of sildenafil's pharmacologic activity. [1][67][131] The N-demethylated metabolite, the major circulating metabolite, has a phosphodiesterase selectivity profile similar to that of sildenafil and an in vitro potency for PDE type 5 of approximately 50% of the parent drug.

• Sildenafil tablets can cause a sudden drop in blood pressure if combined with nitrates.
• Proper hydration helps ensure the effectiveness of sildenafil tablets.
• Reading the patient information leaflet helps understand the correct use of sildenafil.

[1][116][131] Sildenafil is eliminated mainly in the feces as metabolites following oral administration. [1][67][91][116][131] In healthy adults and those with ED, approximately 80% of an oral dose is excreted as metabolites in feces and 13% is excreted in urine. Importance of instructing 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 erectile dysfunction (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 concomitant administration may lead to symptomatic hypotension in some patients.

• Sildenafil tablets are available by prescription and should not be purchased from unverified sources.
• Store sildenafil tablets at room temperature away from moisture and heat.
• Do not split or crush sildenafil tablets unless specified by a doctor.

[1]Inform patients taking sildenafil for erectile dysfunction and sildenafil generic 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.

Dose (mg)	Typical Usage Frequency	Onset of Action	Duration of Effect
25	As needed, 1 time/day	30-60 minutes	Up to 4 hours
50	As needed, 1-2 times/day	30-60 minutes	Up to 6 hours
100	As needed, 1 time/day	30-60 minutes	Up to 4-6 hours

[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 erectile dysfunction that the drug offers no protection against sexually transmitted diseases and patients should use necessary protective measures to guard against such diseases, including the human immunodeficiency virus (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 blood pressure (e.g., dizziness, lightheadedness, fainting). [1] Monitor blood pressure when administering sildenafil in combination with blood pressure lowering 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]Advise patient to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. [1]Inform patients of other important precautionary information.

Misconception	Reality	Explanation
Sildenafil cures erectile dysfunction	It does not cure, only treats symptoms	Helps achieve an erection, not a cure
Takes effect immediately	Usually takes 30-60 minutes	Depends on individual and food intake
Only for older men	Used by men of various ages	Suitable for adult men of different ages

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

What special precautions should I follow?

[1]Inform patients of other important precautionary information. 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 © Copyright, 1959-2026, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Dosage for erectile dysfunction (ED)

The American Society of Health-System Pharmacists, Inc. represents that the database provided hereunder as formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. makes no representations or warranties, express or implied, including, but not limited to, any implied warranty or merchantability and/or fitness for a particular purpose, with respect to such database and specifically disclaims all such warranties and representations. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the database if provided for informational purposes only.

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

The entire monograph for a drug should be reviewed for a throrough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug in the database. The information contained in the database is not a substitute for medical care or treatment by a licensed health care provider. 1 Pulmonary arterial pressure Show forest plot 2 PaO2 in mmHg (absolute values) Show forest plot 2.3 After 6 to 7 hours of treatment 2.4 After 24 to 25 hours of treatment 2.5 After 72 hours or at the end of treatment 3 Mean arterial blood pressure in mmHg Show forest plot 3.2 At the end of therapy 4 All‐cause mortality Show forest plot Risk Difference (M‐H, Fixed, 95% CI) 5 Oxygenation index (absolute values) Show forest plot 5.3 After 6 to 7 hours of treatment 5.4 After 24 to 25 hours of treatment 5.5 After 30 hours of treatment 5.6 After 36 hours of treatment 5.7 After 72 hours or at the end of treatment 6 Change in oxygenation index Show forest plot 6.2 After 24 hours of treatment 6.3 After 30 hours of treatment 6.4 After 36 hours of treatment 7 A‐a DO2 difference Show forest plot 7.2 At 6 to 7 hours of treatment 7.3 At 24 to 25 hours of treament 7.4 At 72 hours or at the end of treatment 8 Mean airway pressure Show forest plot 8.2 At 6 to 7 hours of treatment 8.3 At 24 to 25 hours of treatment 8.4 At 72 hours or at the end of treatment Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

12.1 Mechanism of Action

[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 concomitant administration may lead to symptomatic hypotension in some patients. [1]Inform patients taking sildenafil for erectile dysfunction and sildenafil generic 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.

#6 Tadalafil(Cialis)

[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 erectile dysfunction that the drug offers no protection against sexually transmitted diseases and patients should use necessary protective measures to guard against such diseases, including the human immunodeficiency virus (HIV). [1]Instruct the patient to seek medical attention immediately if they take too much sildenafil.

Addyi (filbanserin)

[1]Inform patients of the risk of symptomatic low blood pressure (e.g., dizziness, lightheadedness, fainting). [1] Monitor blood pressure when administering sildenafil in combination with blood pressure lowering 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]Advise patient to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. \* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name © Copyright, 1959-2026, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. The American Society of Health-System Pharmacists, Inc. represents that the database provided hereunder as formulated with a reasonable standard of care, and in conformity with professional standards in the field.

What should I do if I forget a dose?

[1][4][91][127][130][249] Administration with a high-fat meal delays GI absorption, with a reduction in peak plasma concentrations of about 29% and a delay in time to peak plasma concentrations of about 60 minutes; the extent of absorption is not affected. Sildenafil appears to be widely distributed in the body. [1][4][67][116][131] Sildenafil and its major circulating N-desmethyl metabolite are each approximately 96% bound to plasma proteins; protein binding reportedly is independent of plasma concentration. [1][67][91][116][131] Sildenafil is distributed to a limited extent in semen following oral administration, with less than 0.001% of a single dose appearing in semen 90 minutes after dosing in healthy individuals. [1][67] Such concentrations are unlikely to cause any effects in sexual partners exposed to the semen.

Allergy warning

[67] Plasma sildenafil concentrations appear to decline in a biphasic manner following oral administration, with a terminal elimination half-life of about 4 hours (range: 3-5 hours). [1][4][67][91][116][127][130][131] Sildenafil is metabolized principally via hepatic cytochrome P-450 (CYP) microsomal isoenzymes 3A4 (major route) and 2C9 (minor route). [1][26][67][91][131] Plasma concentrations of the active N-desmethyl metabolite are approximately 40% of those observed with sildenafil, and the metabolite reportedly accounts for about 20% of sildenafil's pharmacologic activity. [1][67][131] The N-demethylated metabolite, the major circulating metabolite, has a phosphodiesterase selectivity profile similar to that of sildenafil and an in vitro potency for PDE type 5 of approximately 50% of the parent drug. [1][116][131] Sildenafil is eliminated mainly in the feces as metabolites following oral administration.

Erectile dysfunction

[1][67][91][116][131] In healthy adults and those with ED, approximately 80% of an oral dose is excreted as metabolites in feces and 13% is excreted in urine. Importance of instructing 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 erectile dysfunction (Viagra) and pulmonary arterial hypertension (Revatio®). [1] Advise patients taking Viagra® not to take Revatio® or other PDE type 5 inhibitors. The American Society of Health-System Pharmacists, Inc. makes no representations or warranties, express or implied, including, but not limited to, any implied warranty or merchantability and/or fitness for a particular purpose, with respect to such database and specifically disclaims all such warranties and representations. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the database if provided for informational purposes only. The entire monograph for a drug should be reviewed for a throrough understanding of the drug's actions, uses and side effects.

5.7 Priapism

[67] No pharmacokinetic interaction has been observed between warfarin, a CYP2C9 substrate, and sildenafil. Sildenafil is a selective inhibitor of phosphodiesterases (PDEs), with the greatest selectivity for PDE type 5, the principal isoenzyme of PDE involved in the metabolism of cyclic guanosine monophosphate (cGMP) to GMP in the corpora cavernosa of the penis. [1][2][4][5][7][8][10][24][27][33][41][42][54][56][57][67][87][88][91][131] Sildenafil has 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] During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpora cavernosa. [1][2][4][56][67][91][131] By selectively inhibiting PDE type 5, sildenafil causes accumulation of cGMP in various tissues.

Serious Side Effects

[1][2][4][5][31][33][34][41][42][56][57][67][91][131] Because sildenafil potentiates the accumulation of cGMP rather than stimulating its production, the drug is effective only when cGMP production in the penis is increased by sexual arousal. [34][91][131] Sildenafil at recommended doses has no effect on erectile function in the absence of sexual stimulation. [1][4][33][34][91][127][130][131][132] Sildenafil also exhibits some activity against other PDE isoenzymes. [1][4][5][31][44][57][67][87][88] In vitro, sildenafil is about 10 times more active against PDE type 5 than against PDE type 6, greater than 70-80 times more active against PDE type 5 than against PDE type 1, greater than 1000 times more active against PDE type 5 than against PDE types 2 and 4, and 4000 times more active against PDE type 5 than against PDE type 3. [1][4][27][31][45][52][55][57][67][87][88] The duration of erectile responsiveness (i.e., the time period in which adequate sexual stimulation can produce an erection) with oral sildenafil has been reported to be approximately 2 hours, with some penile responsiveness persisting for up to 4 hours after oral administration.

Pulmonary hypertension

[1] In the largest clinical study published to date, the onset and duration of action of oral sildenafil were not reported. [33][34] In most other placebo-controlled studies in which improvement in erection was determined by penile plethysmography, the erectile effect was determined at a fixed time of 60 minutes after an oral dose of the drug. Sildenafil is rapidly absorbed following oral administration; the mean absolute bioavailability is 41% (range, 25-63%). [1][4][56][67][91][116][249] Although studies indicate that more than 90% of an oral sildenafil dose is absorbed from the GI tract, the drug undergoes extensive metabolism in the GI mucosa during absorption and on first pass through the liver, with only about 40% of a dose reaching systemic circulation unchanged. [1][4][56][67][91][116][131][249] Pharmacokinetics of the drug (as determined by peak plasma concentrations or AUC) are dose proportional over the single-dose range of 1.25-200 mg.[1][4][56][91][116][131] Peak plasma concentrations of sildenafil and its active N-desmethyl metabolite are achieved within 30-120 (median: 60) minutes following oral administration in fasting adults. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug in the database. The information contained in the database is not a substitute for medical care or treatment by a licensed health care provider. 1 Pulmonary arterial pressure Show forest plot 2 PaO2 in mmHg (absolute values) Show forest plot 2.3 After 6 to 7 hours of treatment 2.4 After 24 to 25 hours of treatment 2.5 After 72 hours or at the end of treatment 3 Mean arterial blood pressure in mmHg Show forest plot 3.2 At the end of therapy 4 All‐cause mortality Show forest plot Risk Difference (M‐H, Fixed, 95% CI) 5 Oxygenation index (absolute values) Show forest plot 5.3 After 6 to 7 hours of treatment 5.4 After 24 to 25 hours of treatment 5.5 After 30 hours of treatment 5.6 After 36 hours of treatment 5.7 After 72 hours or at the end of treatment 6 Change in oxygenation index Show forest plot 6.2 After 24 hours of treatment 6.3 After 30 hours of treatment 6.4 After 36 hours of treatment 7 A‐a DO2 difference Show forest plot 7.2 At 6 to 7 hours of treatment 7.3 At 24 to 25 hours of treament 7.4 At 72 hours or at the end of treatment 8 Mean airway pressure Show forest plot 8.2 At 6 to 7 hours of treatment 8.3 At 24 to 25 hours of treatment 8.4 At 72 hours or at the end of treatment