Sildenafil User Reviews & Ratings

[1][31][67][131] In addition, AUC and peak plasma concentrations of the N-demethylated metabolite are 200 and 79% greater, respectively, than those in individuals with normal renal function. In patients with severe renal impairment (creatinine clearance less than 30 mL/minute), consider reducing the initial dose of sildenafil to 25 mg.[1] The most common adverse effects (>=2%) of sildenafil used for the treatment of ED include headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, and rash.

Renal Dose Adjustments

[1][31][67][131] In addition, AUC and peak plasma concentrations of the N-demethylated metabolite are 200 and 79% greater, respectively, than those in individuals with normal renal function. In patients with severe renal impairment (creatinine clearance less than 30 mL/minute), consider reducing the initial dose of sildenafil to 25 mg.[1] The most common adverse effects (>=2%) of sildenafil used for the treatment of ED include headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, and rash. Sildenafil is metabolized principally via hepatic cytochrome P-450 (CYP) microsomal isoenzymes 3A4 (major route) and 2C9 (minor route). [1][91][131] Inhibitors and inducers of these isoenzymes may reduce or increase sildenafil clearance, respectively. In vitro studies indicate that sildenafil is a weak inhibitor of the CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4.

Platelet-aggregation Inhibitors

[1][26][67][250] Sildenafil is not expected to affect the pharmacokinetics of substrates of these CYP enzymes at clinically relevant concentrations. The possibility that any drug that inhibits CYP3A4 may interact with sildenafil should be considered. [1][67] In some cases, a reduction in sildenafil dosage is recommended. Clinically important pharmacokinetic interactions have been reported with several antiretroviral agents that inhibit CYP3A4 (e.g., ritonavir, saquinavir) and can potentially result in an increase in sildenafil-associated adverse effects. The possibility that any drug that induces CYP3A4 may interact with sildenafil should be considered.

The Bottom Line

Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics when the drug was used concomitantly with CYP2D6 inhibitors such as selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. [1] [26][67] At clinically relevant concentrations, the manufacturer states that it is unlikely that sildenafil will alter the clearance of drugs metabolized by these isoenzymes. A minor route of metabolism of sildenafil is through the CYP2C9 isoenzyme. [1][67][250] Although some clinicians state that the possibility of an interaction between sildenafil and drugs metabolized by CYP2C9 should be considered, there was no evidence of appreciable inhibition of CYP2C9-mediated (e.g., tolbutamide, warfarin) or CYP3A4-mediated (e.g., ritonavir, saquinavir) metabolism by sildenafil in clinical studies. **Antacids:**Single doses of an aluminum and magnesium hydroxide-containing antacid did not affect the oral bioavailability of sildenafil. Sildenafil is metabolized principally via hepatic cytochrome P-450 (CYP) microsomal isoenzymes 3A4 (major route) and 2C9 (minor route). [1][91][131] Inhibitors and inducers of these isoenzymes may reduce or increase sildenafil clearance, respectively. In vitro studies indicate that sildenafil is a weak inhibitor of the CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. [1][26][67][250] Sildenafil is not expected to affect the pharmacokinetics of substrates of these CYP enzymes at clinically relevant concentrations. The possibility that any drug that inhibits CYP3A4 may interact with sildenafil should be considered.

• Sildenafil 60mg is one of several doses available.
• Your doctor may adjust the dose based on response.
• Use only the dose prescribed to you.
• Do not self-adjust the medication without medical advice.

[1][67] In some cases, a reduction in sildenafil dosage is recommended.

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Clinically important pharmacokinetic interactions have been reported with several antiretroviral agents that inhibit CYP3A4 (e.g., ritonavir, saquinavir) and can potentially result in an increase in sildenafil-associated adverse effects.

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Cimetidine: Plasma sildenafil concentrations increased by approximately 56% in healthy individuals who received a single 50-mg oral dose of the drug concomitantly with a single oral dose of cimetidine (800 mg), a nonspecific inhibitor of the cytochrome P-450 mixed-function oxidase system. [1][67] Population pharmacokinetic analysis of data from clinical trials indicates that cimetidine reduces sildenafil clearance when these drugs are administered concomitantly. [1][139] Some clinicians recommend that a lower initial sildenafil dose buy sildenafil citrate online canada (25 mg) be considered in patients with ED receiving cimetidine. Concomitant use of any form of organic nitrate (e.g., nitroglycerin), including recreational use of inhaled nitrites (amyl nitrate or nitrite, ''poppers''), with sildenafil is contraindicated due to the potential pharmacodynamic interaction (increased hypotensive effect). However, the American College of Cardiology (ACC) and American Heart Association (AHA) recognize that use of organic nitrates and nitrites in patients receiving sildenafil may not be completely avoidable, provided sufficient time has elapsed between use of sildenafil and administration of the nitrate or nitrite.

Special Populations

[67] Although it is not known how much time must elapse between use of sildenafil and administration of a nitrate or nitrite, pharmacokinetic data suggest that these latter agents should not be given within 24 hours of sildenafil administration because an exaggerated hypotensive response is likely; plasma sildenafil concentrations are substantially lower 24 hours after a dose than peak concentrations. [1][29][31][67] The point at which nitrates or nitrites can be given safely is unclear, and therefore the drugs should be avoided unless, in the view of the treating clinician, the benefits outweigh the risks. If consideration is given to administering a nitrate or nitrite beyond 24 hours after sildenafil use, the response to the initial doses must be monitored carefully and proper facilities for fluid and vasopressor (e.g., α-adrenergic agonists) support must be readily available to prevent acute ischemic episodes. [67][159] In patients in whom clearance of sildenafil and/or its metabolites may be prolonged (e.g., those with hepatic [e.g., cirrhosis] or severe renal impairment [e.g., creatinine clearance less than 30 mL/minute], those receiving a potent inhibitor of CYP3A4, geriatric patients older than 65 years of age), a more extended period of time between use of sildenafil and administration of a nitrate or nitrite may be necessary. [1][67][154] In either case, a short-acting nitrate formulation that can be titrated readily (e.g., IV nitroglycerin) is preferred and such use should be accompanied by close hemodynamic monitoring.

Therapies for Erectile Dysfunction

Sildenafil 50 mg did not potentiate the hypotensive effect of alcohol (0.5 g/kg) in healthy individuals (mean maximum blood alcohol concentrations of 0.08% achieved). Sildenafil has systemic vasodilatory effects and may augment the blood pressure-lowering effect of other antihypertensive agents. [1] Hypotensive responses secondary to sildenafil use in patients receiving antihypertensive therapy have been observed. 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. The AUC of the active metabolite, N-desmethyl sildenafil, was increased 62% by loop and potassium-sparing diuretics and 102% by nonspecific β-adrenergic blocking agents; however, the increased active metabolite concentrations sildenafil 50mg tablet are not expected to be clinically important. The possibility that any drug that induces CYP3A4 may interact with sildenafil should be considered. Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics when the drug was used concomitantly with CYP2D6 inhibitors such as selective serotonin-reuptake inhibitors (SSRIs) or tricyclic antidepressants. [1] [26][67] At clinically relevant concentrations, the manufacturer states that it is unlikely that sildenafil will alter the clearance of drugs metabolized by these isoenzymes. A minor route of metabolism of sildenafil is through the CYP2C9 isoenzyme.

• Sildenafil 60mg is used to treat erectile dysfunction.
• It works by relaxing blood vessels to increase blood flow.
• The usual dosing frequency is once a day.
• Do not take more than one dose in 24 hours.

[1][67][250] Although some clinicians state that the possibility of an interaction between sildenafil and drugs metabolized by CYP2C9 should be considered, there was no evidence of appreciable inhibition of CYP2C9-mediated (e.g., tolbutamide, warfarin) or CYP3A4-mediated (e.g., ritonavir, saquinavir) metabolism by sildenafil in clinical studies. **Antacids:**Single doses of an aluminum and magnesium hydroxide-containing antacid did not affect the oral bioavailability of sildenafil. Cimetidine: Plasma sildenafil concentrations increased by approximately 56% in healthy individuals who received a single 50-mg oral dose of the drug concomitantly with a single oral dose of cimetidine (800 mg), a nonspecific inhibitor of the cytochrome P-450 mixed-function oxidase system. [1][67] Population pharmacokinetic analysis of data from clinical trials indicates that cimetidine reduces sildenafil clearance when these drugs are administered concomitantly.

In case of emergency/overdose

[1][85][136][137][139] In these patients receiving ritonavir and sildenafil, plasma concentrations at 24 hours were approximately 200 ng/mL compared with 5 ng/mL when sildenafil was given alone. [1][139] Sildenafil is only a weak inhibitor of CYP3A4 and CYP2D6 isoenzymes and single doses of the drug had no effect on steady-state saquinavir or ritonavir pharmacokinetics in healthy adults.

Antihypertensive and α-Adrenergic Blocking Agents

[1][139] Some clinicians recommend that a lower initial sildenafil dose buy sildenafil citrate online canada (25 mg) be considered in patients with ED receiving cimetidine. Concomitant use of any form of organic nitrate (e.g., nitroglycerin), including recreational use of inhaled nitrites (amyl nitrate or nitrite, ''poppers''), with sildenafil is contraindicated due to the potential pharmacodynamic interaction (increased hypotensive effect). However, the American College of Cardiology (ACC) and American Heart Association (AHA) recognize that use of organic nitrates and nitrites in patients receiving sildenafil may not be completely avoidable, provided sufficient time has elapsed between use of sildenafil and administration of the nitrate or nitrite.

Side Effect	Severity	Frequency	Notes
Headache	Mild to moderate	Common	Usually subsides within hours
Flushing	Mild	Frequent	Redness of face or neck
Nasal Congestion	Mild	Common	Stuffiness in nasal passages

[67] Although it is not known how much time must elapse between use of sildenafil and administration of a nitrate or nitrite, pharmacokinetic data suggest that these latter agents should not be given within 24 hours of sildenafil administration because an exaggerated hypotensive response is likely; plasma sildenafil concentrations are substantially lower 24 hours after a dose than peak concentrations. [1][29][31][67] The point at which nitrates or nitrites can be given safely is unclear, and therefore the drugs should be avoided unless, in the view of the treating clinician, the benefits outweigh the risks. If consideration is given to administering a nitrate or nitrite beyond 24 hours after sildenafil use, the response to the initial doses must be monitored carefully and proper facilities for fluid and vasopressor (e.g., α-adrenergic agonists) support must be readily available to prevent acute ischemic episodes. [67][159] In patients in whom clearance of sildenafil and/or its metabolites may be prolonged (e.g., those with hepatic [e.g., cirrhosis] or severe renal impairment [e.g., creatinine clearance less than 30 mL/minute], those receiving a potent inhibitor of CYP3A4, geriatric patients older than 65 years of age), a more extended period of time between use of sildenafil and administration of a nitrate or nitrite may be necessary. [1][67][154] In either case, a short-acting nitrate formulation that can be titrated readily (e.g., IV nitroglycerin) is preferred and such use should be accompanied by close hemodynamic monitoring. Sildenafil 50 mg did not potentiate the hypotensive effect of alcohol (0.5 g/kg) in healthy individuals (mean maximum blood alcohol concentrations of 0.08% achieved). Sildenafil has systemic vasodilatory effects and may augment the blood pressure-lowering effect of other antihypertensive agents. [1] Hypotensive responses secondary to sildenafil use in patients receiving antihypertensive therapy have been observed.

• Avoid use if you have recent heart attack or stroke.
• Discuss your full medical history with your doctor.
• Be aware of the potential for allergic reactions.
• Discontinue use and consult a doctor if adverse effects occur.

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. The AUC of the active metabolite, N-desmethyl sildenafil, was increased 62% by loop and potassium-sparing diuretics and 102% by nonspecific β-adrenergic blocking agents; however, the increased active metabolite concentrations sildenafil 50mg tablet are not expected to be clinically important. Additive hypotensive effects may be anticipated when PDE type 5 inhibitors are administered concurrently with α-adrenergic blocking agents (e.g., terazosin, doxazosin, tamsulosin). [1] Stepwise increases in the dosage of the α-adrenergic blocking agent may further lower blood pressure when a PDE type 5 inhibitor is administered concurrently.

Side Effects for Revatio

Additive hypotensive effects may be anticipated when PDE type 5 inhibitors are administered concurrently with α-adrenergic blocking agents (e.g., terazosin, doxazosin, tamsulosin). [1] Stepwise increases in the dosage of the α-adrenergic blocking agent may further lower blood pressure when a PDE type 5 inhibitor is administered concurrently. [1] In several placebo-controlled crossover studies in patients with benign prostatic hyperplasia receiving doxazosin (4 or 8 mg daily) under steady-state conditions, administration of a single dose of sildenafil (50 or 100 mg) resulted in symptomatic hypotension (e.g., dizziness, lightheadedness, nausea, headache, fatigue) in some patients, occurring within approximately 0.5-4 hours of sildenafil administration. [1] Although symptomatic hypotension occurred in a few patients who received sildenafil 50 or 100 mg, syncope was not reported during these drug interaction studies. [1] Caution is advised when PDE type 5 inhibitors are used concomitantly with an α-adrenergic blocking agent.

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[1] Patients should be hemodynamically stable on α-adrenergic blocking therapy prior to initiating therapy with a PDE type 5 inhibitor. [1] Patients who demonstrate hemodynamic instability on α-adrenergic blocking therapy are at increased risk of symptomatic hypotension with concomitant use of PDE type 5 inhibitors. [1] In patients who are hemodynamically stable on α-adrenergic blocking therapy, PDE type 5 inhibitors should be initiated at the lowest recommended dose. [1] Conversely, in patients taking an optimized dose of a PDE type 5 inhibitor, therapy with an α-adrenergic blocking agent should be initiated at the lowest recommended dosage. [1] Incremental increases in the dosage of the α-adrenergic blocking agent during such concomitant therapy may be associated with a further lowering of blood pressure.

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[1] Safety of combination therapy with an α-adrenergic blocking agent may be affected by other variables, including intravascular volume depletion and concomitant use of other antihypertensive agents. Following administration of a single 100-mg sildenafil dose in hypertensive patients whose blood pressure was controlled with amlodipine 5 or 10 mg daily, mean supine blood pressure was reduced (systolic by 8 mm Hg, diastolic by 7 mm Hg). [1][29][154] The greatest decreases in supine systolic and diastolic blood pressures following sildenafil administration were in patients with the highest baseline blood pressures, suggesting that the likelihood of a hypotensive episode during combined use with amlodipine is low. While reported experience with use of sildenafil in HIV-infected patients receiving antiretroviral therapy is limited, clinically important pharmacokinetic interactions have been demonstrated when the drug was used concomitantly with ritonavir and saquinavir. [1][240] Pretreatment with saquinavir (1200-mg liquid-filled capsules [no longer commercially available in the US] 3 times daily) or ritonavir (500 mg twice daily) followed by a single dose of sildenafil (100 mg) increased sildenafil AUC by 210 or 1000%, respectively, and sildenafil peak plasma concentrations by 140 or 300%, respectively. [1] In several placebo-controlled crossover studies in patients with benign prostatic hyperplasia receiving doxazosin (4 or 8 mg daily) under steady-state conditions, administration of a single dose of sildenafil (50 or 100 mg) resulted in symptomatic hypotension (e.g., dizziness, lightheadedness, nausea, headache, fatigue) in some patients, occurring within approximately 0.5-4 hours of sildenafil administration. [1] Although symptomatic hypotension occurred in a few patients who received sildenafil 50 or 100 mg, syncope was not reported during these drug interaction studies.

• Sildenafil has been shown to improve erectile function.
• It was originally developed for pulmonary hypertension.
• Unexpected side effects should be reported to a doctor.
• Avoid using other ED medications simultaneously.

[1] Caution is advised when PDE type 5 inhibitors are used concomitantly with an α-adrenergic blocking agent. [1] Patients should be hemodynamically stable on α-adrenergic blocking therapy prior to initiating therapy with a PDE type 5 inhibitor. [1] Patients who demonstrate hemodynamic instability on α-adrenergic blocking therapy are at increased risk of symptomatic hypotension with concomitant use of PDE type 5 inhibitors. [1] In patients who are hemodynamically stable on α-adrenergic blocking therapy, PDE type 5 inhibitors should be initiated at the lowest recommended dose. [1] Conversely, in patients taking an optimized dose of a PDE type 5 inhibitor, therapy with an α-adrenergic blocking agent should be initiated at the lowest recommended dosage. [1] Incremental increases in the dosage of the α-adrenergic blocking agent during such concomitant therapy may be associated with a further lowering of blood pressure. [1] Safety of combination therapy with an α-adrenergic blocking agent may be affected by other variables, including intravascular volume depletion and concomitant use of other antihypertensive agents. Following administration of a single 100-mg sildenafil dose in hypertensive patients whose blood pressure was controlled with amlodipine 5 or 10 mg daily, mean supine blood pressure was reduced (systolic by 8 mm Hg, diastolic by 7 mm Hg). [1][29][154] The greatest decreases in supine systolic and diastolic blood pressures following sildenafil administration were in patients with the highest baseline blood pressures, suggesting that the likelihood of a hypotensive episode during combined use with amlodipine is low. While reported experience with use of sildenafil in HIV-infected patients receiving antiretroviral therapy is limited, clinically important pharmacokinetic interactions have been demonstrated when the drug was used concomitantly with ritonavir and saquinavir. [1][240] Pretreatment with saquinavir (1200-mg liquid-filled capsules [no longer commercially available in the US] 3 times daily) or ritonavir (500 mg twice daily) followed by a single dose of sildenafil (100 mg) increased sildenafil AUC by 210 or 1000%, respectively, and sildenafil peak plasma concentrations by 140 or 300%, respectively. [1][85][136][137][139] In these patients receiving ritonavir and sildenafil, plasma concentrations at 24 hours were approximately 200 ng/mL compared with 5 ng/mL when sildenafil was given alone. [1][139] Sildenafil is only a weak inhibitor of CYP3A4 and CYP2D6 isoenzymes and single doses of the drug had no effect on steady-state saquinavir or ritonavir pharmacokinetics in healthy adults.