4 CONTRAINDICATIONS

[1][8][33][131] In part, the absence of an effect on sexual desire may be attributed to the fact that men enrolling in ED studies generally have a near-normal level of sexual desire upon study entry. [33][107][130][131] Improvement in erectile function sufficient for successful intercourse can be achieved with sildenafil in a substantial percentage of patients with ED, and the strength and duration of erection achieved with the drug in such patients approached those achieved in untreated healthy men.

Sildenafil also has been effective in a limited number of men with temporary ED associated with the stress of providing a sperm sample (e.g., for intrauterine insemination or in vitro fertilization during assisted reproduction). [143] In men with a history of such temporary dysfunction, planned use of sildenafil for subsequent attempts at obtaining a sperm specimen may improve attainment of an erection adequate for self-stimulated ejaculation. While most males with ED respond to oral sildenafil therapy, treatment failures do occur; pooled data from various placebo-controlled, dose-response, or open-label studies (25-100 mg for 6-12 months) indicate that up to 5% of patients discontinued therapy because of lack of effectiveness. [1][7][33][69][93][104][107][128][131][132][163][165] Information on the long-term effects of sildenafil is limited, and thus the optimum duration of therapy is not known. [1][33][81][128][132] In clinical studies, sildenafil was used in patients ranging in age from 19-87 years of age with a duration of ED averaging 5 years. [1] In several long-term and open-label studies, sildenafil remained effective for at least 0.5-4 years, with no evidence of tachyphylaxis during long-term use, and current evidence indicates that continued therapy is necessary as long as the condition persists (i.e., sildenafil is not a cure for ED). The safety and efficacy of sildenafil in combination with other treatments for ED have not been established. [1] Such combined therapy may further lower blood pressure and is not recommended by the manufacturer. With the availability of orally active and convenient vasoactive (erectogenic) therapies (e.g., selective phosphodiesterase [PDE] type 5 inhibitors such as sildenafil, tadalafil, avanafil, and vardenafil), most experts (e.g., the American Urological Association [AUA]) now consider these drugs to be first-line therapies for a broad range of patients with ED. Because PDE type 5 inhibitors are administered orally, they are likely to be more acceptable to men with ED than other vasoactive therapies (e.g., intracavernosal injections, intraurethral suppositories) or mechanical or prosthetic devices.

5.7 Priapism

With the availability of orally active and convenient vasoactive (erectogenic) therapies (e.g., selective phosphodiesterase [PDE] type 5 inhibitors such as sildenafil, tadalafil, avanafil, and vardenafil), most experts (e.g., the American Urological Association [AUA]) now consider these drugs to be first-line therapies for a broad range of patients with ED. Because PDE type 5 inhibitors are administered orally, they are likely to be more acceptable to men with ED than other vasoactive therapies (e.g., intracavernosal injections, intraurethral suppositories) or mechanical or prosthetic devices. [26][33][81][94][107][602] Alternative therapies (e.g., intracavernosal or intraurethral vasoactive agents, vacuum constriction devices) may be considered for patients who fail to respond to, or are not candidates for, first-line therapy (e.g., patients who require nitrate therapy). [144][155][161][189][601] Ultimately, the choice of therapy for ED should be individualized, taking into account patient response, tolerability and safety; administration considerations, cost and patient reimbursement factors; experience and judgment of the clinician; and individual patient and partner preference, expectations, and satisfaction. [33][65][81][101][189][601][602] PDE type 5 inhibitors are effective only in the presence of adequate sexual stimulation.

Clinical Uses

[1][189][602] Prior to proceeding to alternative therapies in patients reporting failure of selective PDE type 5 inhibitor therapy, an evaluation to determine whether there was an adequate trial should be undertaken. [34][104][602] Treatment failure may also be attributed to sildenafil 60mg incorrect use of PDE type 5 inhibitor therapy (e.g., lack of sexual stimulation, medication taken with a large meal). [189] The possibility that another selective PDE type 5 inhibitor therapy may be effective should be considered in patients who fail an adequate trial with one drug. [189][601][602] Although differences in the pharmacokinetics of these drugs (onset and duration) may exist, data currently are insufficient to support the superiority of one selective PDE type 5 inhibitor over another. Administer sildenafil tablets orally without regard to meals; however, administration with a high-fat meal may delay the onset of action. [26][33][81][94][107][602] Alternative therapies (e.g., intracavernosal or intraurethral vasoactive agents, vacuum constriction devices) may be considered for patients who fail to respond to, or are not candidates for, first-line therapy (e.g., patients who require nitrate therapy). [144][155][161][189][601] Ultimately, the choice of therapy for ED should be individualized, taking into account patient response, tolerability and safety; administration considerations, cost and patient reimbursement factors; experience and judgment of the clinician; and individual patient and partner preference, expectations, and satisfaction. [33][65][81][101][189][601][602] PDE type 5 inhibitors are effective only in the presence of adequate sexual stimulation.

[1][189][602] Prior to proceeding to alternative therapies in patients reporting failure of selective PDE type 5 inhibitor therapy, an evaluation to determine whether there was an adequate trial should be undertaken. [34][104][602] Treatment failure may also be attributed to sildenafil 60mg incorrect use of PDE type 5 inhibitor therapy (e.g., lack of sexual stimulation, medication taken with a large meal). [189] The possibility that another selective PDE type 5 inhibitor therapy may be effective should be considered in patients who fail an adequate trial with one drug. [189][601][602] Although differences in the pharmacokinetics of these drugs (onset and duration) may exist, data currently are insufficient to support the superiority of one selective PDE type 5 inhibitor over another.

Before Using

[1] [117][131] Administer the drug approximately 1 hour before anticipated sexual activity. [1][28][33][81][91][93][94][102][105][118][130][132][161][602][603] Sexual stimulation is required for response to therapy. Sildenafil tablets should be stored at 20-25°C (excursions permitted to 15-30°C). For the treatment of erectile dysfunction (ED), the recommended initial dosage of sildenafil is 50 mg orally as needed approximately 1 hour before anticipated sexual activity. [1][28][33][81][91][93][94][102][105][118][130][132][161] The maximum recommended dosing frequency is once per day.

Drug forms and administration

[1] The dose may be taken anywhere from 4 hours to 30 minutes before sexual activity. [1] Peak plasma concentrations are achieved within 30-120 minutes (median 60 minutes) when taken on an empty stomach; the erectile response is diminished at 4 hours compared with 2 hours after administration. Based on effectiveness and tolerance, the dose subsequently may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg (maximum frequency once per day). [1][28][33][91][93][94][105][161] Evidence from dose-ranging studies indicates that erectile response is greater at 50- or 100-mg doses than at 25 mg.[1][28][33][130][131] Dosage of sildenafil, including both the dose and frequency of use, must be individualized carefully according to the patient's tolerance and erectile response. Concomitant use with protease inhibitors (e.g., ritonavir): An initial sildenafil dose of 25 mg is recommended in patients receiving protease inhibitors. Administer sildenafil tablets orally without regard to meals; however, administration with a high-fat meal may delay the onset of action. [1] [117][131] Administer the drug approximately 1 hour before anticipated sexual activity. [1][28][33][81][91][93][94][102][105][118][130][132][161][602][603] Sexual stimulation is required for response to therapy. Sildenafil tablets should be stored at 20-25°C (excursions permitted to 15-30°C). For the treatment of erectile dysfunction (ED), the recommended initial dosage of sildenafil is 50 mg orally as needed approximately 1 hour before anticipated sexual activity. [1][28][33][81][91][93][94][102][105][118][130][132][161] The maximum recommended dosing frequency is once per day. [1] The dose may be taken anywhere from 4 hours to 30 minutes before sexual activity. [1] Peak plasma concentrations are achieved within 30-120 minutes (median 60 minutes) when taken on an empty stomach; the erectile response is diminished at 4 hours compared with 2 hours after administration. Based on effectiveness and tolerance, the dose subsequently may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg (maximum frequency once per day).

• Sildenafil citrate was originally developed for hypertension.
• It was later approved for erectile dysfunction treatment.
• Brand names include Viagra and Revatio.

[1][28][33][91][93][94][105][161] Evidence from dose-ranging studies indicates that erectile response is greater at 50- or 100-mg doses than at 25 mg.[1][28][33][130][131] Dosage of sildenafil, including both the dose and frequency of use, must be individualized carefully according to the patient's tolerance and erectile response. Concomitant use with protease inhibitors (e.g., ritonavir): An initial sildenafil dose of 25 mg is recommended in patients receiving protease inhibitors. [1][200] When used concomitantly, do not exceed a maximum single sildenafil dose of 25 mg in a 48 hour period and monitor for adverse effects.

• Typical sildenafil dose ranges from 25 to 100 mg.
• It should be taken 30-60 minutes before activity.
• Do not exceed one dose within 24 hours.

In patients with hepatic impairment (e.g., cirrhosis), consider reducing the initial dose of sildenafil to 25 mg.[1] In patients with severe renal impairment (creatinine clearance <30 mL/minute), consider reducing the initial dose of sildenafil to 25 mg.[1] In patients >= 65 years of age, consider reducing the initial dose of sildenafil to 25 mg.[1] Concomitant use of organic nitrates (e.g., nitroglycerin) in any form (e.g., orally, sublingually, transmucosally, parenterally), either regularly or intermittently. [1] Therapy for erectile dysfunction (ED), including sildenafil, generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. [1] The evaluation of ED should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. Sildenafil doses of 25-100 mg reduce the maximum supine sildenafil 100mg blue pill systolic/diastolic blood pressure by an average of about 8.4/5.5 mm Hg within 1-2 hours after administration of the drug in healthy adults, returning to baseline values within 4-8 hours after a dose.

12.2 Pharmacodynamics

[1][200] When used concomitantly, do not exceed a maximum single sildenafil dose of 25 mg in a 48 hour period and monitor for adverse effects. In patients with hepatic impairment (e.g., cirrhosis), consider reducing the initial dose of sildenafil to 25 mg.[1] In patients with severe renal impairment (creatinine clearance <30 mL/minute), consider reducing the initial dose of sildenafil to 25 mg.[1] In patients >= 65 years of age, consider reducing the initial dose of sildenafil to 25 mg.[1] Concomitant use of organic nitrates (e.g., nitroglycerin) in any form (e.g., orally, sublingually, transmucosally, parenterally), either regularly or intermittently. [1] Therapy for erectile dysfunction (ED), including sildenafil, generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. [1] The evaluation of ED should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. Sildenafil doses of 25-100 mg reduce the maximum supine sildenafil 100mg blue pill systolic/diastolic blood pressure by an average of about 8.4/5.5 mm Hg within 1-2 hours after administration of the drug in healthy adults, returning to baseline values within 4-8 hours after a dose.

Study 2: Sildenafil citrate with Doxazosin

Clinicians should consider whether patients with underlying cardiovascular disease could be affected adversely by the vasodilatory activity of selective PDE type 5 inhibitor therapy, especially in combination with sexual activity. Because there are no controlled clinical data establishing the safety and efficacy of sildenafil in the following subpopulations of patients with ED, the drug should be used with caution in those with a recent (within 6 months) myocardial infarction, stroke, or life-threatening arrhythmia; in those with resting hypotension (blood pressure less than 90/50 mm Hg) or hypertension (blood pressure exceeding 170/110 mm Hg); and in those with cardiac failure or coronary artery disease causing unstable angina. [1][31][101][127][144][154][155][159] The possibility of a hypotensive reaction in patients receiving a selective PDE type 5 inhibitor concomitantly with antihypertensive drug therapy should be considered. [28][31][67] The risk of an undesired hypotensive response is of particular concern in patients with congestive heart failure and a borderline low blood volume and low blood pressure status as well as in patients with left-ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis), those with severely impaired autonomic control of blood pressure, and in those who are receiving a complex, multidrug antihypertensive regimen. [1][67] Some experts state that monitoring of blood pressure during initiation of sildenafil therapy may be useful in identifying patients who may have an undesirable hypotensive response to the drug and is recommended for patients receiving a multidrug antihypertensive regimen and in those with congestive heart failure who have a borderline low blood volume because of concern about the potential consequences on blood pressure. Clinicians should consider whether patients with underlying cardiovascular disease could be affected adversely by the vasodilatory activity of selective PDE type 5 inhibitor therapy, especially in combination with sexual activity.

2.1 Recommended Dosage in Adults

[28][67][159] In patients with severe renal impairment, concomitant use of sildenafil and antihypertensive agents should be undertaken with caution. Nonarteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely during postmarketing experience in temporal association with use of all PDE type 5 inhibitors for the treatment of ED. [1][190][191][192][196][197] Most, but not all, of these patients had underlying anatomic or vascular risk factors for the development of NAION, including but not limited to low cup-to-disc ratio (''crowded" optic disc), age (older than 50 years), diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. [1][191][192][196] Available data suggest that the annual incidence of NAION in the general population of men 50 years of age or older is 2.5-11.8 cases per 100,000. [1] Results of an observational study in patients with recent, episodic PDE type 5 inhibitor use (typical of ED treatment) suggest an approximately two-fold increase in the risk of NAION, with a risk estimate of 2.15 within 5 half-lives of such use.

Does Viagra work the first time you use it?

Because there are no controlled clinical data establishing the safety and efficacy of sildenafil in the following subpopulations of patients with ED, the drug should be used with caution in those with a recent (within 6 months) myocardial infarction, stroke, or life-threatening arrhythmia; in those with resting hypotension (blood pressure less than 90/50 mm Hg) or hypertension (blood pressure exceeding 170/110 mm Hg); and in those with cardiac failure or coronary artery disease causing unstable angina. [1][31][101][127][144][154][155][159] The possibility of a hypotensive reaction in patients receiving a selective PDE type 5 inhibitor concomitantly with antihypertensive drug therapy should be considered. [28][31][67] The risk of an undesired hypotensive response is of particular concern in patients with congestive heart failure and a borderline low blood volume and low blood pressure status as well as in patients with left-ventricular outflow obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis), those with severely impaired autonomic control of blood pressure, and in those who are receiving a complex, multidrug antihypertensive regimen. [1][67] Some experts state that monitoring of blood pressure during initiation of sildenafil therapy may be useful in identifying patients who may have an undesirable hypotensive response to the drug and is recommended for patients receiving a multidrug antihypertensive regimen and in those with congestive heart failure who have a borderline low blood volume because of concern about the potential consequences on blood pressure.

[28][67][159] In patients with severe renal impairment, concomitant use of sildenafil and antihypertensive agents should be undertaken with caution. Nonarteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely during postmarketing experience in temporal association with use of all PDE type 5 inhibitors for the treatment of ED. [1][190][191][192][196][197] Most, but not all, of these patients had underlying anatomic or vascular risk factors for the development of NAION, including but not limited to low cup-to-disc ratio (''crowded" optic disc), age (older than 50 years), diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, and smoking. [1][191][192][196] Available data suggest that the annual incidence of NAION in the general population of men 50 years of age or older is 2.5-11.8 cases per 100,000. [1] Results of an observational study in patients with recent, episodic PDE type 5 inhibitor use (typical of ED treatment) suggest an approximately two-fold increase in the risk of NAION, with a risk estimate of 2.15 within 5 half-lives of such use.

2.2 Use with Food

[1][8][33][131] In part, the absence of an effect on sexual desire may be attributed to the fact that men enrolling in ED studies generally have a near-normal level of sexual desire upon study entry. [33][107][130][131] Improvement in erectile function sufficient for successful intercourse can be achieved with sildenafil in a substantial percentage of patients with ED, and the strength and duration of erection achieved with the drug in such patients approached those achieved in untreated healthy men. Sildenafil also has been effective in a limited number of men with temporary ED associated with the stress of providing a sperm sample (e.g., for intrauterine insemination or in vitro fertilization during assisted reproduction). [143] In men with a history of such temporary dysfunction, planned use of sildenafil for subsequent attempts at obtaining a sperm specimen may improve attainment of an erection adequate for self-stimulated ejaculation. While most males with ED respond to oral sildenafil therapy, treatment failures do occur; pooled data from various placebo-controlled, dose-response, or open-label studies (25-100 mg for 6-12 months) indicate that up to 5% of patients discontinued therapy because of lack of effectiveness.

Mild side effects

[1][7][33][69][93][104][107][128][131][132][163][165] Information on the long-term effects of sildenafil is limited, and thus the optimum duration of therapy is not known. [1][33][81][128][132] In clinical studies, sildenafil was used in patients ranging in age from 19-87 years of age with a duration of ED averaging 5 years. [1] In several long-term and open-label studies, sildenafil remained effective for at least 0.5-4 years, with no evidence of tachyphylaxis during long-term use, and current evidence indicates that continued therapy is necessary as long as the condition persists (i.e., sildenafil is not a cure for ED). The safety and efficacy of sildenafil in combination with other treatments for ED have not been established. [1] Such combined therapy may further lower blood pressure and is not recommended by the manufacturer.