In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh class A and B), sildenafil clearance was reduced, resulting in increases in AUC (84%) and C max(47%) compared to age-matched volunteers with no hepatic impairment.
- Sildenafil citrate is primarily used to treat erectile dysfunction.
- 120 mg is a high dosing level and should only be used under medical supervision.
- The typical starting dose for sildenafil is 50 mg; 120 mg exceeds standard recommendations.
- High doses can increase the risk of side effects such as headaches and low blood pressure.
- Sildenafil works by relaxing blood vessels in the penis to facilitate an erection.
- Overdose of sildenafil citrate can cause severe hypotension and vision disturbances.
Patients with severe hepatic impairment (Child-Pugh class C) have not been studied. Sildenafil metabolism is principally mediated by the CYP3A (major route) and CYP2C9 (minor route) cytochrome P450 isoforms. Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A (IC50 greater than 150 µM). Sildenafil is not expected to affect the pharmacokinetics of compounds which are substrates of these CYP enzymes at clinically relevant concentrations.
- 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.
The effects of other drugs on sildenafil pharmacokinetics and the effects of sildenafil on the exposure to other drugs are shown in Figure 7 and Figure 8, respectively.
5.7 Combination with other PDE-5 inhibitors
At the end of 1 year, 94% of these patients were still alive. Additionally, walk distance and functional class status appeared to be stable in patients taking sildenafil tablets. Without a control group, these data must be interpreted cautiously.Study 2 (Sildenafil tablets co-administered with epoprostenol)A randomized, double-blind, placebo controlled study (Study 2) was conducted in 267 patients with PAH who were taking stable doses of intravenous epoprostenol. Patients had to have a mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg and a pulmonary capillary wedge pressure (PCWP) less than or equal to 15 mmHg at rest via right heart catheterization within 21 days before randomization, and a baseline 6-minute walk test distance greater than or equal to 100 meters and less than or equal to 450 meters (mean 349 meters). Patients were randomized to placebo or sildenafil tablets (in a fixed titration starting from 20 mg, to 40 mg and then 80 mg, three times a day) and all patients continued intravenous epoprostenol therapy.At baseline patients had PPH (80%) or PAH secondary to CTD (20%);WHO functional class I (1%), II (26%), III (67%), or IV (6%); and the mean age was 48 years, 80% were female, and 79% were Caucasian.There was a statistically significant greater increase from baseline in 6-minute walk distance at Week 16 (primary endpoint) for the sildenafil tablets group compared with the placebo group.
Usual Geriatric Dose for:
The mean change from baseline at Week 16 (last observation carried forward) was 30 meters for the sildenafil tablets group compared with 4 meters for the placebo group giving an adjusted treatment difference of 26 meters (95% CI: 10.8, 41.2) (p = 0.0009).Patients on sildenafil tablets achieved a statistically significant reduction in mPAP compared to those on placebo. A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favor of sildenafil tablets (95% CI: -5.7, -2.1) (p = 0.00003).Time to clinical worsening of PAH was defined as the time from randomization to the first occurrence of a clinical worsening event (death, lung transplantation, initiation of bosentan therapy, or clinical deterioration requiring a change in epoprostenol therapy). Table 4 displays the number of patients with clinical worsening events in Study 2. Kaplan-Meier estimates and a stratified log-rank test demonstrated that placebo-treated patients were 3 times more likely to experience a clinical worsening event than the sildenafil tablets-treated patients and that sildenafil tablets-treated patients experienced a significant delay in time to clinical worsening versus placebo-treated patients (p = 0.0074). Kaplan-Meier plot of time to clinical worsening is presented in Figure 11.Figure 11.
Drug Interactions
Kaplan-Meier Plot of Time (in Days) to Clinical Worsening of PAH (in Study 2)Improvements in WHO functional class for PAH were also demonstrated in subjects on sildenafil tablets compared to placebo. More than twice as many sildenafil tablets-treated patients (36%) as the placebo-treated patients (14%) showed an improvement in at least one functional New York Heart Association (NYHA) class for PAH.Study 3 (Sildenafil tablets monotherapy (1 mg, 5 mg, and 20 mg three times a day))A randomized, double-blind, parallel dose study (Study 3) was planned in 219 patients with PAH. Effects of Other Drugs on Sildenafil Pharmacokinetics Figure 8 Effects of Sildenafil on Other Drugs Population pharmacokinetic analysis of data from patients in clinical trails indicated an approximately 30% reduction in sildenafil clearance when it was co-administered with mild/moderate CYP3A inhibitors and an approximately 34% reductions in sildenafil clearance when co-administered with beta-blockers. This concentration range covers the same increased sildenafil exposure observed in specifically-designed drug interaction studies with CYP3A inhibitors (except for potent inhibitors such as ketoconazole, itraconazole, and ritonavir). Concomitant administration of potent CYP3A inducers is expected to cause substantial decreases in plasma levels of sildenafil. Population pharmacokinetic analysis of data from patients in clinical trials indicated an approximately 3-fold the sildenafil clearance when it was co-administered with mild CYP3A inducers. The mean reduction of sildenafil (80 mg three times a day) bioavailability when co-administered with epoprostenol was 28%, resulting in about 22% lower mean average steady state concentrations. Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%. NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilitySildenafil was not carcinogenic when administered to rats for up to 24 months at 60 mg/kg/day, a dose resulting in total systemic exposure (AUC) to unbound sildenafil and its major metabolite 33- and 37- times, for male and female rats respectively, the human exposure at the RHD of 20 mg three times a day. Sildenafil was not carcinogenic when administered to male and female mice for up to 21 and 18 months, respectively, at doses up to a maximally tolerated level of 10 mg/kg/day, a dose equivalent to the RHD on a mg/m 2basis.Sildenafil was negative in in vitrobacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitrohuman lymphocytes and in vivomouse micronucleus assays to detect clastogenicity.There was no impairment of fertility in male or female rats given up to 60 mg sildenafil/kg/day, a dose producing a total systemic exposure (AUC) to unbound sildenafil and its major metabolite of 19- and 38- times for males and females, respectively, the human exposure at the RHD of 20 mg three times a day. Sildenafil was not carcinogenic when administered to rats for up to 24 months at 60 mg/kg/day, a dose resulting in total systemic exposure (AUC) to unbound sildenafil and its major metabolite 33- and 37- times, for male and female rats respectively, the human exposure at the RHD of 20 mg three times a day. Sildenafil was not carcinogenic when administered to male and female mice for up to 21 and 18 months, respectively, at doses up to a maximally tolerated level of 10 mg/kg/day, a dose equivalent to the RHD on a mg/m 2basis. There was no impairment of fertility in male or female rats given up to 60 mg sildenafil/kg/day, a dose producing a total systemic exposure (AUC) to unbound sildenafil and its major metabolite of 19- and 38- times for males and females, respectively, the human exposure at the RHD of 20 mg three times a day. CLINICAL STUDIES Studies of Adults with Pulmonary Arterial HypertensionStudy 1 (Sildenafil tablets monotherapy (20 mg, 40 mg, and 80 mg three times a day))A randomized, double-blind, placebo-controlled study of sildenafil tablets (Study 1) was conducted in 277 patients with PAH (defined as a mean pulmonary artery pressure of greater than or equal to 25 mmHg at rest with a pulmonary capillary wedge pressure less than 15 mmHg).
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Viagra Generic | 200mg | 30 + 2 Pills | 83.07€ 79.11€ | |
| Kamagra Polo | 100mg | 84 + 4 Pills | 244.49€ 232.85€ | |
| Viagra Generic | 150mg | 10 Pills | 36.73€ 34.98€ | |
| Kamagra Soft Tabs | 100mg | 120 + 6 Pills | 311.78€ 296.93€ | |
| Viagra Generic | 25mg | 180 + 6 Pills | 154.93€ 147.55€ | |
| Viagra Generic | 150mg | 30 + 2 Pills | 72.32€ 68.88€ | |
| Viagra Generic | 200mg | 60 + 4 Pills | 125.19€ 119.23€ | |
| Viagra Generic | 50mg | 270 + 8 Pills | 198.48€ 189.03€ | |
| Kamagra | 100mg | 32 Pills | 121.24€ 115.47€ | |
| Viagra Generic | 200mg | 180 + 10 Pills | 277.56€ 264.34€ | |
| Kamagra Soft Tabs | 100mg | 84 + 4 Pills | 233.05€ 221.95€ | |
| Viagra Generic | 150mg | 180 + 10 Pills | 236.46€ 225.20€ | |
| Kamagra Polo | 100mg | 60 + 4 Pills | 189.39€ 180.37€ | |
| Viagra Generic | 150mg | 120 + 8 Pills | 177.58€ 169.12€ | |
| Viagra Generic | 50mg | 60 + 4 Pills | 83.93€ 79.93€ | |
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| Kamagra Oral Jelly | 100mg | 63 + 7 Sachets | 224.18€ 213.50€ |
Patients were predominantly World Health Organization (WHO) functional classes II–III.
Cobra-120 Compared With Other ED Options
Is 20 mg of sildenafil effective for ED?
How are Sildenafil Citrate Tablets used?
Allowed background therapy included a combination of anticoagulants, digoxin, calcium channel blockers, diuretics, and oxygen.
| Use Case | Description | Dosage Recommendations | Special Considerations |
|---|---|---|---|
| Erectile Dysfunction (ED) | To improve blood flow to the penis during arousal | 120 mg as prescribed | Not for use with nitrates |
| Pulmonary Arterial Hypertension | Off-label for vasodilation in lungs | Under doctor guidance | Monitor blood pressure |
| Off-label Use in Sexual Dysfunction | Sometimes used in other sexual dysfunctions | As prescribed | Limited evidence for other uses |
| Enhancement of Exercise Capacity | Occasionally used in sports medicine | Not approved | Risk of adverse effects |
The use of prostacyclin analogues, endothelin receptor antagonists, and arginine supplementation were not permitted. Subjects who had failed to respond to bosentan were also excluded.
Benefits You Can Expect
Sildenafil was not carcinogenic when administered to male and female mice for up to 21 and 18 months, respectively, at doses up to a maximally tolerated level of 10 mg/kg/day, a dose equivalent to the RHD on a mg/m 2basis. There was no impairment of fertility in male or female rats given up to 60 mg sildenafil/kg/day, a dose producing a total systemic exposure (AUC) to unbound sildenafil and its major metabolite of 19- and 38- times for males and females, respectively, the human exposure at the RHD of 20 mg three times a day. CLINICAL STUDIES Studies of Adults with Pulmonary Arterial HypertensionStudy 1 (Sildenafil tablets monotherapy (20 mg, 40 mg, and 80 mg three times a day))A randomized, double-blind, placebo-controlled study of sildenafil tablets (Study 1) was conducted in 277 patients with PAH (defined as a mean pulmonary artery pressure of greater than or equal to 25 mmHg at rest with a pulmonary capillary wedge pressure less than 15 mmHg). Patients were predominantly World Health Organization (WHO) functional classes II–III. Allowed background therapy included a combination of anticoagulants, digoxin, calcium channel blockers, diuretics, and oxygen.
Drugs Affecting Gastric Acidity
The use of prostacyclin analogues, endothelin receptor antagonists, and arginine supplementation were not permitted. Subjects who had failed to respond to bosentan were also excluded. Patients with left ventricular ejection fraction less than 45% or left ventricular shortening fraction less than 0.2 also were not studied.Patients were randomized to receive placebo (n=70) or sildenafil tablets, 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. They had either primary pulmonary hypertension (PPH) (63%), PAH associated with CTD (30%), or pfizer sildenafil 100 PAH following surgical repair of left-to-right congenital heart lesions (7%). The study population consisted of 25% men and 75% women with a mean age of 49 years (range: 18–81 years) and baseline 6-minute walk distance between 100 and 450 meters (mean 343).The primary efficacy endpoint was the change from baseline at week 12 (at least 4 hours after the last dose) in the 6-minute walk distance.
Warnings for people with certain health conditions
Placebo-corrected mean increases in walk distance of 45–50 meters were observed with all doses of sildenafil tablets. These increases were significantly different from placebo, but the sildenafil tablets dose groups were not different from each other (see Figure 9), indicating no additional clinical benefit from doses higher than 20 mg three times a day. The improvement in walk distance was apparent after 4 weeks of treatment and was maintained at week 8 and week 12.Figure 9. Change from Baseline in 6-Minute Walk Distance (meters) at Weeks 4, 8, and 12 in Study 1: Mean (95% Confidence Interval)Figure 10 displays subgroup efficacy analyses in Study 1 for the change from baseline in 6-Minute Walk Distance at Week 12 including baseline walk distance, disease etiology, functional class, gender, age and hemodynamic parameters.Figure 10. Placebo-Corrected Change From Baseline in 6-Minute Walk Distance (meters) at Week 12 by study subpopulation in Study 1: Mean (95% Confidence Interval)Key:PAH = pulmonary arterial hypertension; CTD = connective tissue disease; PH = pulmonary hypertension; PAP = pulmonary arterial pressure; PVRI = pulmonary vascular resistance index; TID = three times daily.Of the 277 treated patients, 259 entered a long-term, uncontrolled extension study. Patients with left ventricular ejection fraction less than 45% or left ventricular shortening fraction less than 0.2 also were not studied.Patients were randomized to receive placebo (n=70) or sildenafil tablets, 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. They had either primary pulmonary hypertension (PPH) (63%), PAH associated with CTD (30%), or pfizer sildenafil 100 PAH following surgical repair of left-to-right congenital heart lesions (7%). The study population consisted of 25% men and 75% women with a mean age of 49 years (range: 18–81 years) and baseline 6-minute walk distance between 100 and 450 meters (mean 343).The primary efficacy endpoint was the change from baseline at week 12 (at least 4 hours after the last dose) in the 6-minute walk distance. Placebo-corrected mean increases in walk distance of 45–50 meters were observed with all doses of sildenafil tablets. These increases were significantly different from placebo, but the sildenafil tablets dose groups were not different from each other (see Figure 9), indicating no additional clinical benefit from doses higher than 20 mg three times a day. The improvement in walk distance was apparent after 4 weeks of treatment and was maintained at week 8 and week 12.Figure 9.
What is Generic Viagra?
In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh class A and B), sildenafil clearance was reduced, resulting in increases in AUC (84%) and C max(47%) compared to age-matched volunteers with no hepatic impairment. Patients with severe hepatic impairment (Child-Pugh class C) have not been studied. Sildenafil metabolism is principally mediated by the CYP3A (major route) and CYP2C9 (minor route) cytochrome P450 isoforms. Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A (IC50 greater than 150 µM). Sildenafil is not expected to affect the pharmacokinetics of compounds which are substrates of these CYP enzymes at clinically relevant concentrations.
Missed Dose
The effects of other drugs on sildenafil pharmacokinetics and the effects of sildenafil on the exposure to other drugs are shown in Figure 7 and Figure 8, respectively. Effects of Other Drugs on Sildenafil Pharmacokinetics Figure 8 Effects of Sildenafil on Other Drugs Population pharmacokinetic analysis of data from patients in clinical trails indicated an approximately 30% reduction in sildenafil clearance when it was co-administered with mild/moderate CYP3A inhibitors and an approximately 34% reductions in sildenafil clearance when co-administered with beta-blockers. This concentration range covers the same increased sildenafil exposure observed in specifically-designed drug interaction studies with CYP3A inhibitors (except for potent inhibitors such as ketoconazole, itraconazole, and ritonavir). Concomitant administration of potent CYP3A inducers is expected to cause substantial decreases in plasma levels of sildenafil. Population pharmacokinetic analysis of data from patients in clinical trials indicated an approximately 3-fold the sildenafil clearance when it was co-administered with mild CYP3A inducers.
Related treatment guides
The mean reduction of sildenafil (80 mg three times a day) bioavailability when co-administered with epoprostenol was 28%, resulting in about 22% lower mean average steady state concentrations. Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%. NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of FertilitySildenafil was not carcinogenic when administered to rats for up to 24 months at 60 mg/kg/day, a dose resulting in total systemic exposure (AUC) to unbound sildenafil and its major metabolite 33- and 37- times, for male and female rats respectively, the human exposure at the RHD of 20 mg three times a day. Sildenafil was not carcinogenic when administered to male and female mice for up to 21 and 18 months, respectively, at doses up to a maximally tolerated level of 10 mg/kg/day, a dose equivalent to the RHD on a mg/m 2basis.Sildenafil was negative in in vitrobacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitrohuman lymphocytes and in vivomouse micronucleus assays to detect clastogenicity.There was no impairment of fertility in male or female rats given up to 60 mg sildenafil/kg/day, a dose producing a total systemic exposure (AUC) to unbound sildenafil and its major metabolite of 19- and 38- times for males and females, respectively, the human exposure at the RHD of 20 mg three times a day. Sildenafil was not carcinogenic when administered to rats for up to 24 months at 60 mg/kg/day, a dose resulting in total systemic exposure (AUC) to unbound sildenafil and its major metabolite 33- and 37- times, for male and female rats respectively, the human exposure at the RHD of 20 mg three times a day. Change from Baseline in 6-Minute Walk Distance (meters) at Weeks 4, 8, and 12 in Study 1: Mean (95% Confidence Interval)Figure 10 displays subgroup efficacy analyses in Study 1 for the change from baseline in 6-Minute Walk Distance at Week 12 including baseline walk distance, disease etiology, functional class, gender, age and hemodynamic parameters.Figure 10. Placebo-Corrected Change From Baseline in 6-Minute Walk Distance (meters) at Week 12 by study subpopulation in Study 1: Mean (95% Confidence Interval)Key:PAH = pulmonary arterial hypertension; CTD = connective tissue disease; PH = pulmonary hypertension; PAP = pulmonary arterial pressure; PVRI = pulmonary vascular resistance index; TID = three times daily.Of the 277 treated patients, 259 entered a long-term, uncontrolled extension study. At the end of 1 year, 94% of these patients were still alive. Additionally, walk distance and functional class status appeared to be stable in patients taking sildenafil tablets.
| Country | Approval Status | Maximum Allowed Dose | Remarks |
|---|---|---|---|
| United States | Approved for ED and pulmonary hypertension | 120 mg | Prescription-only, controlled use |
| European Union | Approved for ED, off-label for other uses | 120 mg | Stringent prescribing regulations |
| Canada | Approved, similar to US | 120 mg | Must be prescribed by healthcare provider |
| Australia | Approved with restrictions | 120 mg | Medical supervision required |
| India | Available, OTC in some regions | 120 mg | Use under medical guidance recommended |
Without a control group, these data must be interpreted cautiously.Study 2 (Sildenafil tablets co-administered with epoprostenol)A randomized, double-blind, placebo controlled study (Study 2) was conducted in 267 patients with PAH who were taking stable doses of intravenous epoprostenol.
- The drug should be taken on an empty stomach for faster effect.
- Use of 120 mg may lead to priapism, a painful, prolonged erection.
- Sildenafil is also used to treat pulmonary arterial hypertension at lower doses.
- Do not exceed prescribed doses to avoid serious adverse reactions.
- Efficacy of sildenafil depends on individual health and possible drug interactions.
- Sildenafil can impair vision temporarily, including blue-tinted vision.
Patients had to have a mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg and a pulmonary capillary wedge pressure (PCWP) less than or equal to 15 mmHg at rest via right heart catheterization within 21 days before randomization, and a baseline 6-minute walk test distance greater than or equal to 100 meters and less than or equal to 450 meters (mean 349 meters). Patients were randomized to placebo or sildenafil tablets (in a fixed titration starting from 20 mg, to 40 mg and then 80 mg, three times a day) and all patients continued intravenous epoprostenol therapy.At baseline patients had PPH (80%) or PAH secondary to CTD (20%);WHO functional class I (1%), II (26%), III (67%), or IV (6%); and the mean age was 48 years, 80% were female, and 79% were Caucasian.There was a statistically significant greater increase from baseline in 6-minute walk distance at Week 16 (primary endpoint) for the sildenafil tablets group compared with the placebo group.
7.1 Nitrates
The mean change from baseline at Week 16 (last observation carried forward) was 30 meters for the sildenafil tablets group compared with 4 meters for the placebo group giving an adjusted treatment difference of 26 meters (95% CI: 10.8, 41.2) (p = 0.0009).Patients on sildenafil tablets achieved a statistically significant reduction in mPAP compared to those on placebo. A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favor of sildenafil tablets (95% CI: -5.7, -2.1) (p = 0.00003).Time to clinical worsening of PAH was defined as the time from randomization to the first occurrence of a clinical worsening event (death, lung transplantation, initiation of bosentan therapy, or clinical deterioration requiring a change in epoprostenol therapy). Table 4 displays the number of patients with clinical worsening events in Study 2.
| Property | Description | Typical Dose | Onset of Action | Duration of Effect | Mechanism of Action |
|---|---|---|---|---|---|
| Bioavailability | Approximately 40% | 120 mg | 30-60 minutes | Up to 6 hours | Inhibits PDE5 enzyme in smooth muscle |
| Half-life | Approximately 4 hours | N/A | N/A | N/A | Enhances nitric oxide signaling |
| Metabolism | Liver via CYP3A4 and CYP2C9 | N/A | N/A | N/A | Prevents cGMP breakdown |
| Excretion | Mainly via feces (80%), urine (13%) | N/A | N/A | N/A | Eliminates unchanged drug |
| Peak Plasma Levels | Achieved within 30-120 minutes | 120 mg | 30 minutes | N/A | Related to dose and absorption rate |
Kaplan-Meier estimates and a stratified log-rank test demonstrated that placebo-treated patients were 3 times more likely to experience a clinical worsening event than the sildenafil tablets-treated patients and that sildenafil tablets-treated patients experienced a significant delay in time to clinical worsening versus placebo-treated patients (p = 0.0074). Kaplan-Meier plot of time to clinical worsening is presented in Figure 11.Figure 11.
- 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.
Kaplan-Meier Plot of Time (in Days) to Clinical Worsening of PAH (in Study 2)Improvements in WHO functional class for PAH were also demonstrated in subjects on sildenafil tablets compared to placebo.
Non-medical use
More than twice as many sildenafil tablets-treated patients (36%) as the placebo-treated patients (14%) showed an improvement in at least one functional New York Heart Association (NYHA) class for PAH.Study 3 (Sildenafil tablets monotherapy (1 mg, 5 mg, and 20 mg three times a day))A randomized, double-blind, parallel dose study (Study 3) was planned in 219 patients with PAH.