[1] Limited data indicate that sildenafil and its active metabolite are present in human milk. [1] There is no information about the effects of sildenafil on the breastfed infant or on milk production. Reproduction studies revealed no evidence of impaired fertility at sildenafil dosages up to 60 mg/kg daily (for 36 days in female rats and 102 days in male rats), a dosage representing more than 25 times the human male AUC.
| Side Effect | Severity | Likelihood | Management Tips |
|---|---|---|---|
| Headache | Mild to moderate | Common | Mild analgesics, hydration |
| Flushing | Mild | Common | Cool environment, stay hydrated |
| Nasal congestion | Mild | Moderately common | Decongestants if necessary |
| Dizziness | Mild | Possible | Avoid sudden movements |
| Visual disturbances | Mild | Rare | Rest and monitor if occurs |
[1] No effect on sperm motility or morphology was noted after a single 100-mg oral sildenafil dose in healthy human adults. Sildenafil for ED (e.g., Viagra®) is not indicated for use in pediatric patients. [1] The manufacturer states that safety and efficacy of sildenafil in children have not been established. The AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45 and 57% higher, respectively, in healthy volunteers >=65 years of age compared to healthy volunteers 18-45 years of age.
5.8 Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell Disease
In patients with any degree of hepatic impairment (e.g. cirrhosis), consider reducing the initial dose of sildenafil to 25 mg.[1] In patients with mild (creatinine clearance 50-80 mL/minute) or moderate (creatinine clearance 30-49 mL/minute) renal impairment, the pharmacokinetics of a single 50-mg oral dose of sildenafil are not altered. [1][31][131] However, in patients with severe (creatinine clearance less than 30 mL/minute) renal impairment, sildenafil clearance is reduced, resulting in AUC and peak plasma concentrations of the parent drug that are approximately double those in age-matched healthy adults. [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.
At what dose is Tadalafil typically prescribed?
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. [1] Clinical studies included patients >=65 years of age (18%) and >=75 years of age (2%); no overall differences in safety and efficacy were observed between older (>=65 years of age) and younger (<65 years of age) patients[1] Because higher plasma levels may increase the incidence of adverse reactions, consider reducing the initial sildenafil dosage to 25 mg in older patients. In patients with hepatic cirrhosis (Child-Pugh class A or B), sildenafil clearance is reduced, resulting in increased AUC (by 85%) and peak plasma concentrations (by 47%) compared with values observed in age-matched healthy adults.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Kamagra Polo | 100mg | 20 Pills | 83.56€ 79.58€ | |
| Viagra Generic | 25mg | 180 + 6 Pills | 154.93€ 147.55€ | |
| Viagra Generic | 100mg | 10 Pills | 28.91€ 27.53€ | |
| Viagra Generic | 150mg | 120 + 8 Pills | 177.58€ 169.12€ | |
| Viagra Generic | 100mg | 60 + 4 Pills | 96.36€ 91.77€ | |
| Viagra Generic | 25mg | 90 + 6 Pills | 105.03€ 100.03€ | |
| Viagra Generic | 25mg | 360 + 10 Pills | 213.68€ 203.50€ | |
| Viagra Generic | 150mg | 270 + 10 Pills | 326.61€ 311.06€ | |
| Viagra Generic | 200mg | 30 + 2 Pills | 83.07€ 79.11€ | |
| Viagra Generic | 50mg | 20 Pills | 40.52€ 38.59€ | |
| Viagra Generic | 150mg | 30 + 2 Pills | 72.32€ 68.88€ | |
| Viagra Generic | 100mg | 180 + 8 Pills | 199.37€ 189.88€ | |
| Viagra Generic | 200mg | 90 + 6 Pills | 170.79€ 162.66€ | |
| Viagra Generic | 25mg | 60 + 4 Pills | 71.99€ 68.56€ | |
| Viagra Generic | 150mg | 60 + 4 Pills | 111.25€ 105.95€ |
[1][31][131] The effect of severe hepatic impairment on the pharmacokinetics of sildenafil has not been evaluated to date. In patients with any degree of hepatic impairment (e.g. cirrhosis), consider reducing the initial dose of sildenafil to 25 mg.[1] In patients with mild (creatinine clearance 50-80 mL/minute) or moderate (creatinine clearance 30-49 mL/minute) renal impairment, the pharmacokinetics of a single 50-mg oral dose of sildenafil are not altered. [1][31][131] However, in patients with severe (creatinine clearance less than 30 mL/minute) renal impairment, sildenafil clearance is reduced, resulting in AUC and peak plasma concentrations of the parent drug that are approximately double those in age-matched healthy adults. [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.
Warnings & Precautions
[1][139] Some clinicians recommend that a lower initial sildenafil dose (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. [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.
How the Combination Treatment Works
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. 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.
Comparing Side Effects
[1] Limited data indicate that sildenafil and its active metabolite are present in human milk. [1] There is no information about the effects of sildenafil on the breastfed infant or on milk production. Reproduction studies revealed no evidence of impaired fertility at sildenafil dosages up to 60 mg/kg daily (for 36 days in female rats and 102 days in male rats), a dosage representing more than 25 times the human male AUC. [1] No effect on sperm motility or morphology was noted after a single 100-mg oral sildenafil dose in healthy human adults. Sildenafil for ED (e.g., Viagra®) is not indicated for use in pediatric patients.
Endothelial friendly
[1] The manufacturer states that safety and efficacy of sildenafil in children have not been established. The AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45 and 57% higher, respectively, in healthy volunteers >=65 years of age compared to healthy volunteers 18-45 years of age. [1] Clinical studies included patients >=65 years of age (18%) and >=75 years of age (2%); no overall differences in safety and efficacy were observed between older (>=65 years of age) and younger (<65 years of age) patients[1] Because higher plasma levels may increase the incidence of adverse reactions, consider reducing the initial sildenafil dosage to 25 mg in older patients. In patients with hepatic cirrhosis (Child-Pugh class A or B), sildenafil clearance is reduced, resulting in increased AUC (by 85%) and peak plasma concentrations (by 47%) compared with values observed in age-matched healthy adults. [1][31][131] The effect of severe hepatic impairment on the pharmacokinetics of sildenafil has not been evaluated to date. 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. [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. 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.
- Medication effectiveness can be impacted by certain health conditions.
- Men should not use sildenafil if they have a history of stroke.
- Sildenafil 10mg can sometimes cause nasal congestion.
- It’s important to report any unusual side effects to your doctor.
- Do not use sildenafil if you are taking other ED medications.
[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 sildenafil 130mg 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.
| Parameter | Value | Notes |
|---|---|---|
| Absorption Rate | Rapid | Peak plasma levels in ~60 minutes |
| Bioavailability | Approximately 40% | Due to first-pass metabolism |
| Half-life | About 4 hours | Time to reduce plasma concentration by half |
| Metabolism | Liver (primarily via CYP3A4) | Enzymatic breakdown |
| Excretion | Mainly feces (~80%) | Some via urine (~13%) |
[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 (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.
Other Comments
[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. 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.
Quality Segment
A minor route of metabolism of sildenafil is through the CYP2C9 isoenzyme. [1][67][250] Although some clinicians state that sildenafil 130mg 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. [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.
- The medication can improve quality of life for men with ED.
- Sildenafil 10mg is often used as a starting dose.
- If no effect, a doctor may adjust the dose accordingly.
- It is not a cure for ED, but a treatment to manage symptoms.
- Use sildenafil only as directed by a healthcare professional.
[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. 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 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).
12.2 Pharmacodynamics
[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 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.
Organic Nitrates, Nitrites, and Nitric Oxide Donors
[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. [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] 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.
- Sildenafil 10mg may be more suitable for older adults with sensitivity.
- Do not take more than one dose in 24 hours.
- Do not mix sildenafil with recreational drugs like poppers.
- Be aware that certain foods and medications can influence its effects.
- Regular medical check-ups are recommended when using sildenafil regularly.
[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.
| Condition | Risk Factors | Recommendations |
|---|---|---|
| Use with nitrates | Severe hypotension, risk of significant blood pressure drop | Avoid combining, consult healthcare provider |
| Severe cardiovascular disease | Risk of adverse cardiovascular events | Use only under medical supervision |
| Liver impairment | Altered metabolism, increased side effects | Dose adjustment or avoid use |
| Retinitis pigmentosa | Potential for increased visual side effects | Use with caution, consult ophthalmologist |
[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.