A starting oral dose of 25 mg should be considered in those patients [ see Dosage and Administration (2.5)Drug Interaction StudiesEffects of Other Drugs on sildenafil tabletsSildenafil metabolism is principally mediated by CYP3A4 (major route) and CYP2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance. The concomitant use of erythromycin or strong CYP3A4 inhibitors (e.g., saquinavir, ketoconazole, itraconazole) as well as the nonspecific CYP inhibitor, cimetidine, is associated with increased plasma levels of sildenafil [ see Dosage and Administration (2.4)].In vivostudies:Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil (50 mg) to healthy volunteers.When a single 100 mg dose of sildenafil tablets was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 160% increase in sildenafil C maxand a 182% increase in sildenafil AUC.
| Side Effect | Severity | Frequency | Comments |
|---|---|---|---|
| Headache | Mild to moderate | Common | Usually temporary |
| Flushing | Mild | Common | Due to vasodilation |
| Nasal Congestion | Mild | Less common | Temporary |
| Dizziness | Mild to moderate | Occasional | Be cautious when standing up |
In addition, in a study performed in healthy male volunteers, co-administration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200 mg tid) with sildenafil (100 mg single dose) resulted in a 140% increase in sildenafil C maxand a 210% increase in sildenafil AUC.
12.2 Pharmacodynamics
The AUC of the active metabolite, N- desmethyl sildenafil, was increased 62% by loop and potassium-sparing diuretics and 102% by nonspecific beta-blockers. These effects on the metabolite are not expected to be of clinical consequence.Effects of sildenafil tablets on Other DrugsIn vitrostudies:Sildenafil is a weak inhibitor of the CYP isoforms sildenafil citrate drug 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 µM). Given sildenafil peak plasma concentrations of approximately 1 µM after recommended doses, it is unlikely that sildenafil will alter the clearance of substrates of these isoenzymes.In vivostudies:No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9.In a study of healthy male volunteers, sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.Sildenafil (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).Sildenafil at steady state, at a dose not approved for the treatment of erectile dysfunction (80 mg t.i.d.) resulted in a 50% increase in AUC and a 42% increase in C maxof bosentan (125 mg b.i.d.). The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
Oral Administration
Sildenafil at recommended doses has no effect in the absence of sexual stimulation. Studies in vitrohave shown that sildenafil is selective for PDE5. This lower selectivity is thought to be buy pills sildenafil the basis for abnormalities related to color vision [ see Clinical Pharmacology (12.2)]. In addition to human corpus cavernosum smooth muscle, PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle. The inhibition of PDE5 in some of these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of NO observed in vitro, an inhibition of platelet thrombus formation in vivoand peripheral arterial-venous dilatation in vivo. A stronger CYP3A4 inhibitor such as ketoconazole or itraconazole could be expected to have greater effect than that seen with saquinavir.
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Viagra Generic | 150mg | 60 + 4 Pills | 111.25€ 105.95€ | |
| Kamagra | 100mg | 32 Pills | 121.24€ 115.47€ | |
| Viagra Generic | 50mg | 360 + 10 Pills | 225.33€ 214.60€ | |
| Kamagra Soft Tabs | 100mg | 32 Pills | 120.11€ 114.39€ | |
| Viagra Generic | 50mg | 90 + 6 Pills | 107.37€ 102.26€ | |
| Viagra Generic | 200mg | 30 + 2 Pills | 83.07€ 79.11€ | |
| Viagra Generic | 25mg | 60 + 4 Pills | 71.99€ 68.56€ | |
| Viagra Generic | 50mg | 270 + 8 Pills | 198.48€ 189.03€ | |
| Viagra Generic | 100mg | 120 + 6 Pills | 149.50€ 142.38€ | |
| Viagra Generic | 200mg | 120 + 8 Pills | 204.80€ 195.05€ | |
| Kamagra Polo | 100mg | 180 + 8 Pills | 446.52€ 425.26€ | |
| Kamagra Soft Tabs | 100mg | 272 + 12 Pills | 593.42€ 565.16€ | |
| Viagra Generic | 150mg | 360 + 10 Pills | 423.48€ 403.31€ | |
| Viagra Generic | 50mg | 60 + 4 Pills | 83.93€ 79.93€ | |
| Viagra Generic | 25mg | 270 + 8 Pills | 184.26€ 175.49€ | |
| Kamagra Soft Tabs | 100mg | 180 + 8 Pills | 425.45€ 405.19€ |
Population pharmacokinetic data from patients in clinical trials also indicated a reduction in sildenafil clearance when it was co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) [ see Dosage and Administration (2.4)and Drug Interactions (7.4)].In another study in healthy male volunteers, co-administration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with sildenafil (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil C maxand a 1000% (11- fold) increase in sildenafil plasma AUC. At 24 hours the plasma levels of sildenafil were still approximately 200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone. This is consistent with ritonavir's marked effects on a broad range of P450 substrates. Sildenafil tablets had no effect on ritonavir pharmacokinetics [ see Dosage and Administration (2.4)and Drug Interactions (7.4)].Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels.In a study of healthy male volunteers, co-administration of sildenafil at steady state (80 mg t.i.d.) with endothelin receptor antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) at steady state (125 mg b.i.d.) resulted in a 63% decrease of sildenafil AUC and a 55% decrease in sildenafil C max.
8.5 Geriatric Use
Effects ofsildenafil tablets on Erectile Response:In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan ®), after sildenafil tablets administration compared with placebo. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours. Effects ofsildenafil tabletson Blood Pressure:Single oral doses of sildenafil (100 mg) administered to healthy volunteers produced decreases in sitting blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8.3/5.3 mmHg). Larger effects were recorded among patients receiving concomitant nitrates [ see Contraindications (4.1)]. Effects ofsildenafil tablets on Blood Pressure When Nitroglycerin is subsequently administered:Based on the pharmacokinetic profile of a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL).
Mechanism of Action
Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely co-administered at this time point [ see Contraindications (4.1)]. Effects ofSildenafil tablets on Blood Pressure When Co-administered with Alpha-Blockers:Three double-blind, placebo-controlled, randomized, two-way crossover studies were conducted to assess the interaction of sildenafil tablets with doxazosin, an alpha-adrenergic blocking agent. In the first study, a single oral dose of sildenafil tablets100 mg or matching placebo was administered in a 2-period crossover design to 4 generally healthy males with benign prostatic hyperplasia (BPH). The mean subject age was 66.5 years. For the 17 subjects who received sildenafil tablets25 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 25 mg sildenafil tablets or matching placebo are shown in Figure 2. Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma levels of sildenafil.Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil.In healthy male volunteers, there was no evidence of a clinically significant effect of azithromycin (500 mg daily for 3 days) on the systemic exposure of sildenafil or its major circulating metabolite.Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers. The AUC of the active metabolite, N- desmethyl sildenafil, was increased 62% by loop and potassium-sparing diuretics and 102% by nonspecific beta-blockers. These effects on the metabolite are not expected to be of clinical consequence.Effects of sildenafil tablets on Other DrugsIn vitrostudies:Sildenafil is a weak inhibitor of the CYP isoforms sildenafil citrate drug 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 µM). Given sildenafil peak plasma concentrations of approximately 1 µM after recommended doses, it is unlikely that sildenafil will alter the clearance of substrates of these isoenzymes.In vivostudies:No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9.In a study of healthy male volunteers, sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.Sildenafil (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).Sildenafil at steady state, at a dose not approved for the treatment of erectile dysfunction (80 mg t.i.d.) resulted in a 50% increase in AUC and a 42% increase in C maxof bosentan (125 mg b.i.d.).
How to Use
The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
- Sildenafil 25mg tablets are available by prescription only.
- They are a common initial dose for men new to the medication.
- Dose adjustments depend on effectiveness and side effects.
- Always inform your doctor about other medications you are taking.
- Overdose symptoms include prolonged erections and chest pain.
- Keep medication out of reach of children and pets.
Sildenafil at recommended doses has no effect in the absence of sexual stimulation. Studies in vitrohave shown that sildenafil is selective for PDE5. This lower selectivity is thought to be buy pills sildenafil the basis for abnormalities related to color vision [ see Clinical Pharmacology (12.2)]. In addition to human corpus cavernosum smooth muscle, PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle. The inhibition of PDE5 in some of these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of NO observed in vitro, an inhibition of platelet thrombus formation in vivoand peripheral arterial-venous dilatation in vivo.
5. Tips
Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours after sildenafil tablets or matching placebo. No severe adverse events potentially related to sildenafil 200 mg blood pressure effects were reported in this group. Of the four subjects who received sildenafil tablets100 mg in the first part of this study, a severe adverse event related to blood pressure effect was reported in one patient (postural hypotension that began 35 minutes after dosing with sildenafil tablets with symptoms lasting for 8 hours), and mild adverse events potentially related to blood pressure effects were reported in two others (dizziness, headache and fatigue at 1 hour after dosing; and dizziness, lightheadedness and nausea at 4 hours after dosing). Both of these subjects were protocol violators, one due to a low baseline standing SBP, and the other due to baseline orthostatic hypotension. In the second study, a single oral dose of sildenafil tablets 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH.
Common Side Effects
The mean subject age in this study was 63.9 years. Twenty subjects received sildenafil tablets 50 mg, but only 19 subjects received matching placebo. This patient had been taking minoxidil, a potent vasodilator, during the study. For the 19 subjects who received both sildenafil tablets and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 50 mg sildenafil tablets or matching placebo are shown in Figure 3. Effects ofsildenafil tablets on Erectile Response:In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan ®), after sildenafil tablets administration compared with placebo.
- Sildenafil 25mg may cause nasal congestion in some users.
- Take note of any changes in vision or sudden loss of vision.
- Consult your doctor if you experience prolonged erections.
- Sildenafil should not be used to enhance athletic performance.
- Combining it with recreational drugs can be dangerous.
- Always review medication instructions before use for safety.
The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours. Effects ofsildenafil tabletson Blood Pressure:Single oral doses of sildenafil (100 mg) administered to healthy volunteers produced decreases in sitting blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8.3/5.3 mmHg).
What are Sildenafil Tablets
A starting oral dose of 25 mg should be considered in those patients [ see Dosage and Administration (2.5)Drug Interaction StudiesEffects of Other Drugs on sildenafil tabletsSildenafil metabolism is principally mediated by CYP3A4 (major route) and CYP2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance. The concomitant use of erythromycin or strong CYP3A4 inhibitors (e.g., saquinavir, ketoconazole, itraconazole) as well as the nonspecific CYP inhibitor, cimetidine, is associated with increased plasma levels of sildenafil [ see Dosage and Administration (2.4)].In vivostudies:Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil (50 mg) to healthy volunteers.When a single 100 mg dose of sildenafil tablets was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 160% increase in sildenafil C maxand a 182% increase in sildenafil AUC. In addition, in a study performed in healthy male volunteers, co-administration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200 mg tid) with sildenafil (100 mg single dose) resulted in a 140% increase in sildenafil C maxand a 210% increase in sildenafil AUC. A stronger CYP3A4 inhibitor such as ketoconazole or itraconazole could be expected to have greater effect than that seen with saquinavir.
Professional resources
Population pharmacokinetic data from patients in clinical trials also indicated a reduction in sildenafil clearance when it was co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) [ see Dosage and Administration (2.4)and Drug Interactions (7.4)].In another study in healthy male volunteers, co-administration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with sildenafil (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil C maxand a 1000% (11- fold) increase in sildenafil plasma AUC. At 24 hours the plasma levels of sildenafil were still approximately 200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone. This is consistent with ritonavir's marked effects on a broad range of P450 substrates. Sildenafil tablets had no effect on ritonavir pharmacokinetics [ see Dosage and Administration (2.4)and Drug Interactions (7.4)].Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels.In a study of healthy male volunteers, co-administration of sildenafil at steady state (80 mg t.i.d.) with endothelin receptor antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) at steady state (125 mg b.i.d.) resulted in a 63% decrease of sildenafil AUC and a 55% decrease in sildenafil C max. Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma levels of sildenafil.Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil.In healthy male volunteers, there was no evidence of a clinically significant effect of azithromycin (500 mg daily for 3 days) on the systemic exposure of sildenafil or its major circulating metabolite.Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers. Larger effects were recorded among patients receiving concomitant nitrates [ see Contraindications (4.1)]. Effects ofsildenafil tablets on Blood Pressure When Nitroglycerin is subsequently administered:Based on the pharmacokinetic profile of a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL). Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely co-administered at this time point [ see Contraindications (4.1)]. Effects ofSildenafil tablets on Blood Pressure When Co-administered with Alpha-Blockers:Three double-blind, placebo-controlled, randomized, two-way crossover studies were conducted to assess the interaction of sildenafil tablets with doxazosin, an alpha-adrenergic blocking agent. In the first study, a single oral dose of sildenafil tablets100 mg or matching placebo was administered in a 2-period crossover design to 4 generally healthy males with benign prostatic hyperplasia (BPH). The mean subject age was 66.5 years. For the 17 subjects who received sildenafil tablets25 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 25 mg sildenafil tablets or matching placebo are shown in Figure 2. Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours after sildenafil tablets or matching placebo. No severe adverse events potentially related to sildenafil 200 mg blood pressure effects were reported in this group. Of the four subjects who received sildenafil tablets100 mg in the first part of this study, a severe adverse event related to blood pressure effect was reported in one patient (postural hypotension that began 35 minutes after dosing with sildenafil tablets with symptoms lasting for 8 hours), and mild adverse events potentially related to blood pressure effects were reported in two others (dizziness, headache and fatigue at 1 hour after dosing; and dizziness, lightheadedness and nausea at 4 hours after dosing).
Pregnancy & Lactation
Both of these subjects were protocol violators, one due to a low baseline standing SBP, and the other due to baseline orthostatic hypotension. In the second study, a single oral dose of sildenafil tablets 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH. The mean subject age in this study was 63.9 years. Twenty subjects received sildenafil tablets 50 mg, but only 19 subjects received matching placebo.
- Sildenafil 25mg can be used for pulmonary arterial hypertension.
- It works by relaxing blood vessels in the lungs.
- Not suitable for everyone; discuss health conditions with your doctor.
- Store tablets in a cool, dry place away from children.
- Do not take more than one dose within 24 hours.
- Report any persistent side effects to your healthcare provider.
This patient had been taking minoxidil, a potent vasodilator, during the study. For the 19 subjects who received both sildenafil tablets and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: The mean profiles of the change from baseline in standing systolic blood pressure in subjects treated with doxazosin in combination with 50 mg sildenafil tablets or matching placebo are shown in Figure 3.
| Condition | Risk | Recommended Action |
|---|---|---|
| Nitrate use (e.g., NTG) | Severe hypotension | Do not take |
| Severe cardiac issues | Increased risk | Consult physician |
| Known hypersensitivity | Allergic reactions | Avoid medication |
| Recent stroke or heart attack | Caution required | Consult doctor |