4 CONTRAINDICATIONS
Secondary endpoints included hemodynamic monitoring, symptom assessment, WHO Functional Class, change in background treatment, and quality of life measurements (n = 234).
| Step | Description | Notes |
|---|---|---|
| Consult a healthcare provider | Discuss suitability and health conditions | Important before use |
| Dose administration | Take with a glass of water, 30-60 min before activity | Avoid heavy or fatty meals |
| Frequency | Do not exceed once per day | Follow prescribed instructions |
| Food interactions | Fatty meals may delay absorption | Better taken on an empty stomach or light meal |
Patients were allocated to one of three sildenafil treatment groups (low, medium, or high) or placebo.
8. Use In Specific Populations
Tmax was estimated at approximately 1 hour. In volunteers with severe (CLcr less than 30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in approximately doubling of AUC and C max compared to age-matched volunteers with no renal impairment. In addition, N-desmethyl metabolite AUC and C max values were significantly increased 200% and 79%, respectively, in patients with severe renal impairment compared to patients with normal renal function. 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 Cmax (47%) compared to age-matched volunteers with no hepatic impairment. Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A (IC 50 greater than 150 µM).
Table 3.5.3: Ascent risk associated with various underlying medical conditions and risk factors
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. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 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/m2 basis. Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity. SUPER-1 (NCT00644605) - Sildenafil citrate monotherapy [20 mg, 40 mg, and 80 mg three times a day] A randomized, double-blind, placebo-controlled study of sildenafil citrate (SUPER-1) was conducted in 277 patients with PAH (defined as a mean pulmonary artery pressure≥25 mmHg at rest with a pulmonary capillary wedge pressure<15 mmHg). Actual doses administered were dependent on body weight (see Table 5).
| Product | Dosage | Quantity + Bonus | Price | |
|---|---|---|---|---|
| Viagra Generic | 100mg | 360 + 10 Pills | 330.21€ 314.49€ | |
| Kamagra Polo | 100mg | 60 + 4 Pills | 189.39€ 180.37€ | |
| Kamagra Polo | 100mg | 120 + 6 Pills | 327.15€ 311.57€ | |
| Viagra Generic | 25mg | 270 + 8 Pills | 184.26€ 175.49€ | |
| Viagra Generic | 50mg | 360 + 10 Pills | 225.33€ 214.60€ | |
| Kamagra Polo | 100mg | 84 + 4 Pills | 244.49€ 232.85€ | |
| Viagra Generic | 25mg | 10 Pills | 25.19€ 23.99€ | |
| Kamagra Polo | 100mg | 180 + 8 Pills | 446.52€ 425.26€ | |
| Viagra Generic | 150mg | 90 + 6 Pills | 147.18€ 140.17€ | |
| Kamagra Oral Jelly | 100mg | 30 + 5 Sachets | 136.20€ 129.71€ | |
| Viagra Generic | 25mg | 180 + 6 Pills | 154.93€ 147.55€ | |
| Kamagra | 100mg | 12 Pills | 55.64€ 52.99€ | |
| Viagra Generic | 150mg | 360 + 10 Pills | 423.48€ 403.31€ |
Treatment Allocation by Dose and Body Weight in Pediatric Study The proportion of patients receiving supportive medicinal products at baseline (anticoagulants, digoxin, calcium channel blockers, diuretics and/or oxygen) was similar in the combined sildenafil treatment group (48%) and the placebo treatment group (42%).
Publication types
Larger effects were recorded among patients receiving concomitant nitrates [see Contraindications (4)] . Sildenafil citrate is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25 to 63%). When sildenafil tablet is taken with a high-fat meal, the rate of absorption is reduced, with a mean delay in T max of 60 minutes and a mean reduction in Cmax of 29%. This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and an in vitro potency for PDE-5 approximately 50% of the parent drug. In healthy volunteers, plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil, so that the metabolite accounts for about 20% of sildenafil's pharmacologic effects.
How does sildenafil work (mechanism of action)?
After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). In patients with PAH, the average steady-state concentrations were 20 to 50% higher when compared to those of healthy volunteers. There was also a doubling of Cmin levels compared to healthy volunteers. Body weight was shown to be a good predictor of drug exposure in children. Sildenafil plasma concentration half-life values were estimated to range from 2.9 to 4.4 hours for a range of 10 to 70 kg of body weight. The primary endpoint was a percentage change in VO2peak from baseline to week 16 assessed by CPET. Mean baseline peak volume of oxygen consumed (VO2) values were similar across the sildenafil treatment groups (17 to 18 ml/kg/min), and slightly higher for the placebo treatment group (20 ml/kg/min). A total of 45% of patients were evaluable for CPET, which comprised those children ≥7 years old and developmentally able to perform the test. Children <7 years were evaluable only for the secondary endpoints.
| Brand Name | Manufacturer | Country of Origin | Description |
|---|---|---|---|
| Viagra | Pfizer | USA | Most well-known brand |
| Revatio | Pfizer | USA | Used for pulmonary hypertension |
| Sildenafil ZYDUS | Zydus Cadila | India | Generic alternative |
| Sildenafil Mylan | Mylan Pharmaceuticals | USA | Generic options |
Mean increases in VO2peak percentage change from baseline at Week 16, were observed with all 3 sildenafil doses (range of 6% to 13%, Figure 6), with little change with placebo (0.5%). Percentage Change from Baseline in VO2Peak: Mean (95% Confidence Intervals) The estimated difference between the combined sildenafil doses and placebo was 8% (95% CI: 0.2 to 16). The results of the main analysis (combined dose groups versus placebo) were not statistically significant (p=0.056).
- Recreational use of sildenafil without prescription is risky.
- The drug is not intended for daily use unless directed.
- Overuse can increase the risk of adverse effects.
- Always discuss health concerns with a healthcare professional.
- Managing stress and anxiety can improve ED symptoms.
- Patients should report persistent side effects promptly.
- Combining sildenafil with certain medications can be dangerous.
- Education on proper use enhances safety and effectiveness.
The estimated difference between the sildenafil medium dose group and placebo was 11±5% (95% CI: 2 to 21).
503A vs 503B
Patients were predominantly WHO Functional Classes II-III. Patients were randomized to receive placebo (n=70) or sildenafil tablet 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. Placebo-Corrected Change From Baseline in 6-Minute Walk Distance (meters) at Week 12 by Study Subpopulation in SUPER-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. SUPER-2 (NCT00159887) Long-term Treatment of PAH In a long-term follow-up of patients who were treated with sildenafil (n=277), K-M estimates of survival at 1, 2, and 3 years were 94%, 88% , and 79%, respectively. Patients were randomized to placebo or sildenafil citrate (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.
Is Viagra prescribed in dosages of 100 mg, 150 mg, or 200 mg?
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. The mean change from baseline at Week 16 (last observation carried forward) was 30 meters for the sildenafil tablet 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). A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favor of sildenafil tablet (95% CI: -5.7, -2.1) (p = 0.00003). 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 sildenafil citrate -treated patients and that sildenafil citrate -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 5. Impact on Hemodynamic Parameters Dose related improvements were observed with PVRI and mPAP.
- Sildenafil tablets 125 mg are often prescribed for pulmonary hypertension.
- The dosage can vary depending on the condition.
- It’s important to maintain open communication with your doctor.
- Alcohol consumption can impair sildenafil’s effectiveness.
- Avoid driving if you experience dizziness or vision problems.
- Use sildenafil exactly as prescribed to avoid complications.
- Do not share medication with others.
- Regular medical check-ups are recommended during use.
Statistically significant PVRI reductions compared to placebo were seen with the sildenafil medium and high dose groups (18% [95% CI: -32% to -2%] and 27% [95% CI: -39% to -14%], respectively) but not the low dose group (2% (95% CI: -20%, 20%).
7.3 Amlodipine
Kaplan-Meier Plot of Time (in Days) to Clinical Worsening of PAH in PACES-1 Improvements in WHO Functional Class for PAH were also demonstrated in patients on sildenafil tablet compared to placebo. More than twice as many sildenafil citrate -treated patients (36%) as placebo-treated patients (14%) showed an improvement in at least one functional New York Heart Association (NYHA) class for PAH. Study A1481243 (NCT00323297) Sildenafil citrate Added to Bosentan Therapy - Lack of Effect on Exercise Capacity A randomized, double-blind, placebo-controlled study was conducted in 103 patients with PAH who were on bosentan therapy for a minimum of 3 months. Patients were randomized to placebo or sildenafil (20 mg three times a day) in combination with sildenafil uk price bosentan (62.5 to 125 mg twice a day). STARTS-1 (NCT00159913) - Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension A total of 234 patients with PAH aged 1 to 17 years were treated in a randomized, double-blind, multi-center, placebo-controlled parallel group, dose-ranging study.
Does sildenafil interact with other medicines (drug interactions)?
Patients (38% male and 62% female) had body weight ≥8 kg and had idiopathic pulmonary arterial hypertension (33%), or PAH associated with congenital heart disease (systemic-to-pulmonary shunt 37%, surgical repair 30%). In this trial, 27% of patients were <7 years old. Patients were WHO Functional Class I (32%), II (51%), III (15%), or IV (0.4%). Patients were naïve for specific PAH therapy and the use of prostacyclin, prostacyclin analogues and endothelin receptor antagonists were not permitted in the study, and neither were arginine supplementation, nitrates, alpha-blockers and potent CYP450 3A4 inhibitors. The primary objective of the study was to assess the effect of Sildenafil citrate on percent change from baseline in PVO2, normalized to body weight, from baseline to week 16 as measured by the Cardiopulmonary Exercise Test (CPET) (patients who were developmentally able to perform the test, n = 115). The sildenafil medium and high dose groups displayed mPAP changes from baseline compared to placebo, of -3.5 mmHg (95% CI: -8.9, 1.9) and -7.3 mmHg (95% CI: -12.4, -2.1), respectively; while the low dose group showed little difference from placebo (difference of 1.6 mmHg [95% CI: -4.5, 7.6]).
| Country | Legal Status | Prescription Required | Notes |
|---|---|---|---|
| USA | Prescription required | Yes | Approved for ED, PH |
| UK | Prescription required | Yes | Prescription necessary |
| India | Over-the-counter in some states | Varies | Varies by region |
| Canada | Prescription required | Yes | Approved for ED and PH |
Improvements were observed with cardiac index with all three sildenafil groups over placebo, 10%, 4%, and 15% for the low, medium, and high dose groups, respectively [see Clinical Pharmacology (12.2)].