14 CLINICAL STUDIES SUPER-1 (NCT00644605) - Sildenafil citrate monotherapy [20 mg, 40 mg, and
| Precaution/Contraindication | Description | Notes |
|---|---|---|
| Nitrate use | Do not take with nitrates for chest pain | Risk of severe hypotension |
| Heart conditions | Consult a doctor if you have cardiovascular issues | Risk of adverse cardiovascular events |
| Liver or kidney impairment | Reduced dosing may be necessary | Altered drug metabolism |
| Drug interactions | Combine with caution; may interact with other meds | Always consult a healthcare provider |
80 mg three times a day]A randomized, double-blind, placebo-controlled study of sildenafil citrate (SUPER-1)
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| Revatio | Pfizer | 20 mg | Global | 15-25 per pill | Blister pack of 30 pills |
| Kamagra | Ajanta Pharma | 50 mg | India, SE Asia | 2-5 per pill | Varies (blister) |
| Sildenafil Original | Local Pharmacies | 50 mg | Local Markets | 12-18 per pill | Bottle/Blister |
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).
5.4 Visual Loss
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.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/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. 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. Patients were predominantly WHO Functional Classes II to III.
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Allowed background therapy included a combination of anticoagulants, digoxin, calcium channel blockers, diuretics, and oxygen.
5.7 Combination with other PDE5 Inhibitors or Other Erectile Dysfunction Therapies
The relationship between these effects and improvements in 6-minute walk distance is unknown. Table 2: Changes from Baseline in Hemodynamic Parameters at Week 12 [mean (95% CI)] for the Sildenafil Citrate 20 mg Three Times a Day and Placebo Group Effects of Sildenafil Citrate on Blood Pressure Single oral doses of sildenafil 100 mg administered to healthy volunteers produced decreases in supine blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8/5 mmHg). Larger effects were recorded among patients receiving concomitant nitrates [see Contraindications (4)]. Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on electrocardiogram (ECG). After chronic dosing of 80 mg three times a day to patients with PAH, no clinically relevant effects on ECG were reported.
Who should not take sildenafil?
After chronic dosing of 80 mg three times a day sildenafil to healthy volunteers, the largest mean change from baseline in supine systolic and supine diastolic blood pressures was a decrease of 9.0 mmHg and 8.4 mmHg, respectively. After chronic dosing of 80 mg three times a day sildenafil to patients with systemic hypertension, the mean change from baseline in systolic and diastolic blood pressures was a decrease of 9.4 mmHg and 9.1 mmHg, respectively. After chronic dosing of 80 mg three times a day sildenafil to patients with PAH, lesser reductions than above in systolic and diastolic blood pressures were observed (a decrease in both of 2 mmHg). At single oral doses of 100 mg and 200 mg, transient dose-related impairment of color discrimination (blue/green) was detected using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. An evaluation of visual function at doses up to 200 mg revealed no effects of sildenafil citrate on visual acuity, intraocular pressure, or pupillometry.
Sildenafil: the science
Pediatric use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil) tablets. However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information. Sildenafil citrate is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25% to 63%). Protein binding is independent of total drug concentrations. Bioequivalence was established between the 20 mg tablet and the 10 mg/mL oral suspension when administered as a 20 mg single oral dose of sildenafil (as citrate). The use of prostacyclin analogues, endothelin receptor antagonists, and arginine supplementation were not permitted.
- The legality of purchasing sildenafil varies by country.
- Online pharmacies may offer sildenafil, but verify their legitimacy.
- White sildenafil tablets are designed for rapid dissolution in the mouth or swallowing.
- Be aware of potential allergic reactions, such as rash or swelling.
- Avoid taking sildenafil with large meals that contain high fat content.
- The effectiveness of sildenafil depends on individual health conditions.
- The American Urological Association provides guidelines on sildenafil use.
- Sildenafil can cause safety concerns in patients with low blood pressure.
- The drug works best when taken approximately one hour before intimacy.
- Use sildenafil solely as directed; misuse can lead to health risks.
- Regular check-ups can help monitor the impact of sildenafil on health.
Patients 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)
Why is this medication prescribed?
Sildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes. Both sildenafil and the active metabolite have terminal half-lives of about 4 hours. After oral 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). Age, gender, race, and renal and hepatic sildenafil film tablet function were included as factors assessed in the population pharmacokinetic model to evaluate sildenafil pharmacokinetics in patients with PAH. None of these factors had a significant impact on sildenafil pharmacokinetics in patients with PAH.
Sildenafil Citrate
In patients with PAH, the average steady-state concentrations were 20% to 50% higher when compared to those of healthy volunteers. Both findings suggest a lower clearance and/or a higher oral bioavailability of sildenafil in patients with PAH compared to healthy volunteers. Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma concentrations of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18 to 45 years). Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively. In volunteers with mild (CLcr = 50 to 80 mL/min) and moderate (CLcr = 30 to 49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of sildenafil (50 mg) was not altered.
How it works for ED
In addition, N-desmethyl metabolite AUC and Cmax 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. 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). or sildenafil citrate 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks.
- Sildenafil tablets are specifically formulated to mitigate potential side effects.
- The tablet's white color is typical for certain dosages or brands.
- Patients with cardiovascular issues should consult a doctor before use.
- Sildenafil is sometimes used to treat certain cases of erectile dysfunction caused by depression medication.
- The effects of sildenafil can be enhanced by reducing alcohol intake.
- Contraceptive methods do not impact sildenafil's effectiveness.
- Sildenafil does not cause spontaneous erections without sexual stimulation.
- It is important to remain seated or relaxed after taking sildenafil.
- The pill’s manufacturing process includes strict quality control protocols.
- Beware of unregulated markets selling unverified sildenafil tablets.
- Follow dosing instructions carefully to prevent overdose or underdose.
They had either primary pulmonary hypertension (PPH) (63%), PAH associated with CTD (30%), or PAH following surgical repair of left-to-right congenital heart lesions (7%).
- Sildenafil tablets are available in various generic versions.
- White sildenafil tablets are often easier to swallow due to their shape.
- The cost of sildenafil varies depending on the brand and dosage.
- Using sildenafil responsibly can improve quality of life for users.
- Not all erectile issues require medication; consult a doctor for underlying causes.
- Sildenafil is not suitable for women or children.
- The drug works by blocking PDE5, enhancing natural erections.
- Physical activity after taking sildenafil can enhance its effectiveness.
- Sildenafil is sometimes used off-label for pulmonary hypertension.
- Proper hydration may help reduce side effects like headaches.
- Patients should report any persistent or severe side effects to a healthcare professional.
The study population consisted of 25% men and 75% women with a mean age of 49 years (range: 18 to 81 years) and baseline 6-minute walk distance between 100
| Country/Region | Legal Status | Regulatory Agency | Prescription Needed | Notes |
|---|---|---|---|---|
| United States | Prescription-only | FDA | Yes | Class II controlled substance |
| European Union | Prescription-required | EMA | Yes | Regulated as prescription drug |
| India | Available both OTC and RX | CDSCO | Prescription recommended | Varies by state |
| Australia | Prescription-only | TGA | Yes | Controlled medicine |
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.
What does Sildenafil Citrate look like?
Sildenafil is not expected to affect the pharmacokinetics of compounds which are substrates of these CYP enzymes at clinically relevant concentrations. The effects of other drugs on sildenafil pharmacokinetics and the effects of sildenafil on the exposure to other drugs are shown in Figure 1 and Figure sildenafil gel 2, respectively. Effects of Other Drugs on Sildenafil Pharmacokinetics Population pharmacokinetic analysis of data from patients in clinical trials 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 strong CYP3A inducers is expected to cause substantial decreases in plasma levels of sildenafil.
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Population pharmacokinetic analysis of data from patients in clinical trials indicated 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. No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9. Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%. 13 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.