Label: SILDENAFIL CITRATE- sildenafil tablet, film coated

[1][33][105][145] In one flexible-dose study (dosage titration and maintenance up to 100 mg), mean scores for number of successful penetrations returned to normal in a subgroup of patients with psychogenic causes of ED; however, mean scores for maintenance of erections during intercourse in these men were lower than in untreated healthy men. [33][34] In a study in men with ED secondary to radical prostatectomy receiving fixed-dose sildenafil (100 mg), response to therapy was greatest in those who had undergone bilateral-nerve-sparing surgery than in those who had undergone unilateral or non-nerve-sparing procedures. [104][127] Pooled data from various clinical trials indicate that sildenafil improved the erections of 43% of patients with ED secondary to radical prostatectomy compared with 15% of those receiving placebo. [1][104] A pooled analysis of 10 placebo-controlled studies of men with severe ED (organic etiology in 60%, psychogenic in 15%, and mixed in 25% of patients) treated with sildenafil (50-100 mg in fixed- or flexible-dose studies) indicated that 48% of the patients usually had erections sufficient for intercourse (score of 4, with 0 being unsuccessful and 5 being almost always successful) after treatment with sildenafil, compared with 8% of those receiving placebo. [76][127] In several randomized, double-blind, placebo-controlled studies in patients receiving sildenafil (flexible doses up to 100 mg or fixed doses ranging from 10-100 mg for 12 weeks) for the treatment of ED attributed to complications of diabetes mellitus, complications of spinal cord injury, or psychogenic causes, 48, 59, or 70% of all attempts at intercourse were successful, respectively, compared with 12, 13, or 29% of all attempts in those receiving placebo. [1][7][8][9][10][25][33][93] In these studies, sildenafil improved several aspects of sexual function including frequency, firmness, and maintenance of erection; frequency of orgasm; satisfaction and enjoyment of intercourse; and overall relationship satisfaction.

• Sildenafil 120 mg is not approved by all regulatory agencies for general use.
• The maximum recommended dose for most individuals is 100 mg.
• Using high doses can lead to increased cardiovascular strain.
• Always inform your doctor of all medications to prevent interactions.
• Sildenafil may cause a sudden drop in blood pressure, especially with certain drugs.
• The medication can be used as part of a treatment plan for erectile dysfunction.

[1][8][9][33][94][107][130][131][142] Pooled data from fixed- and flexible-dose studies indicate that sildenafil (50 or 100 mg) has no effect on sexual desire (i.e., rates of attempted intercourse, which averaged about 2 per week), but the rate of success increased to an average of 1.3 events per patient per week from 0.4 events per week with placebo. [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.

2.2 Use with Food

[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).

Less common

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 sildenafil oral solution 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). 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.

Liver Dose Adjustments

[1][33][105][145] In one flexible-dose study (dosage titration and maintenance up to 100 mg), mean scores for number of successful penetrations returned to normal in a subgroup of patients with psychogenic causes of ED; however, mean scores for maintenance of erections during intercourse in these men were lower than in untreated healthy men. [33][34] In a study in men with ED secondary to radical prostatectomy receiving fixed-dose sildenafil (100 mg), response to therapy was greatest in those who had undergone bilateral-nerve-sparing surgery than in those who had undergone unilateral or non-nerve-sparing procedures. [104][127] Pooled data from various clinical trials indicate that sildenafil improved the erections of 43% of patients with ED secondary to radical prostatectomy compared with 15% of those receiving placebo. [1][104] A pooled analysis of 10 placebo-controlled studies of men with severe ED (organic etiology in 60%, psychogenic in 15%, and mixed in 25% of patients) treated with sildenafil (50-100 mg in fixed- or flexible-dose studies) indicated that 48% of the patients usually had erections sufficient for intercourse (score of 4, with 0 being unsuccessful and 5 being almost always successful) after treatment with sildenafil, compared with 8% of those receiving placebo. [76][127] In several randomized, double-blind, placebo-controlled studies in patients receiving sildenafil (flexible doses up to 100 mg or fixed doses ranging from 10-100 mg for 12 weeks) for the treatment of ED attributed to complications of diabetes mellitus, complications of spinal cord injury, or psychogenic causes, 48, 59, or 70% of all attempts at intercourse were successful, respectively, compared with 12, 13, or 29% of all attempts in those receiving placebo.

2. Custom Packaging and Labeling Options

[1][7][8][9][10][25][33][93] In these studies, sildenafil improved several aspects of sexual function including frequency, firmness, and maintenance of erection; frequency of orgasm; satisfaction and enjoyment of intercourse; and overall relationship satisfaction. [1][8][9][33][94][107][130][131][142] Pooled data from fixed- and flexible-dose studies indicate that sildenafil (50 or 100 mg) has no effect on sexual desire (i.e., rates of attempted intercourse, which averaged about 2 per week), but the rate of success increased to an average of 1.3 events per patient per week from 0.4 events per week with placebo. [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). [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.

Dosage at a Glance

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).

Organic Nitrates, Nitrites, and Nitric Oxide Donors

[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. 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] 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).

Non-medical use

[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 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. 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. 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 sildenafil oral solution 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. [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.

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

[34][104][602] Treatment failure may also be attributed to 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. [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).

• The safety of 120 mg sildenafil is not well-established for all users.
• High-dose sildenafil may cause muscle aches and back pain.
• Alcohol consumption can intensify sildenafil’s side effects.
• Aspirin and blood thinners may increase bleeding risk when combined with sildenafil.
• Patients with heart conditions should seek medical advice before use.
• The drug should not be used in conjunction with other erectile dysfunction medications.

[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.

5.7 Combination with other PDE-5 inhibitors

[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 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.

How should Sildenafil Citrate Tablets be stored?

[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. [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). 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.

Side Effects

[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 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. 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.