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.

Warnings & Precautions

Sildenafil is also marketed as Sildenafil citrate® for erectile dysfunction. Sildenafil citrate, USP is designated chemically as 1-[ [3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate and has the following structural formula: Patients on all Sildenafil citrate doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo in a study with no background vasodilators [Study 1 in Clinical Studies (14)]. Data on other hemodynamic measures for the Sildenafil citrate 20 mg three times a day and placebo dosing regimens is displayed in Table 3. The relationship between these effects and improvements in 6minute walk distance is unknown. mPAP = mean pulmonary arterial pressure; PVR= pulmonary vascular resistance; SVR = systemic vascular resistance; RAP = right atrial pressure; CO = cardiac output; HR = heart rate *The number of patients per treatment group varied slightly for each parameter due to missing assessments.

Sildenafil vs. tadalafil

In another study evaluating lower doses of sildenafil 1 mg, 5 mg and 20 mg, there were no significant differences in the effects on hemodynamic variables between doses. 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). The decrease in blood pressure was most notable approximately 1 to 2 hours after dosing, and was not different from placebo at 8 hours. Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg doses of sildenafil, therefore the effects are not related to dose or plasma levels within this dosage range. Larger effects were recorded among patients receiving concomitant nitrates.

Off-Label Use and Dosage (Adult)

Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant sildenafil tablet manforce 50 mg effects on ECG. After chronic dosing of 80 mg TID to patients with PAH, no clinically relevant effects on ECG were reported. After chronic dosing of 80 mg TID sildenafil to healthy volunteers, the largest mean change from baseline in supine systolic and supine diastolic blood pressures was a decrease of 9 mmHg and 8.4 mmHg, respectively. After chronic dosing of 80 mg TID 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 TID sildenafil to patients with PAH, lesser reductions than above in systolic and diastolic blood pressures were observed (a decrease in both of 2 mmHg). In patients with PAH, however, the ratio of the metabolite to sildenafil is higher.

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Both sildenafil and the active metabolite have terminal half-lives of about 4 hours.

Sildenafil citrate is a medication used primarily for erectile dysfunction.
It works by relaxing blood vessels to increase blood flow.
Sildenafil is also prescribed for pulmonary arterial hypertension.
Common side effects include headache, flushing, and nasal congestion.
It should be taken 30-60 minutes before sexual activity.
Alcohol and high-fat meals can reduce its effectiveness.
Do not take with nitrate medications due to risk of severe hypotension.

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).

Some users report headaches and dizziness after taking sildenafil.
A common side effect is facial flushing and nasal congestion.
Rare side effects include sudden hearing loss or vision loss.
Priapism requires urgent medical attention to prevent tissue damage.
Sudden vision loss should be immediately evaluated by a doctor.
Allergic reactions such as rash, hives, or swelling are possible.
Discontinue use and seek medical help if serious side effects occur.

Age, gender, race, and renal and hepatic function were included as factors assessed in the population pharmacokinetic model to evaluate sildenafil pharmacokinetics in patients with PAH. The dataset available for the population pharmacokinetic evaluation contained a wide range of demographic data and laboratory parameters associated with hepatic and renal function.

Frequently asked questions

There is no FDA guidance one the use of Sildenafil in patients who are immunocompromised. FDA Package Insert for Sildenafil contains no information regarding drug monitoring. There is limited information about the IV Compatibility. In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but rates and severities were increased. In cases of overdose, standard supportive measures should be adopted as required.

Label Warnings

The approximately 4,000-fold selectivity for PDE-5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE-5 compared to PDE6, an enzyme found in the retina and involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels. In addition to pulmonary vascular smooth muscle and the corpus cavernosum, PDE-5 is also found in other tissues including vascular and visceral smooth muscle and in platelets. The inhibition of PDE-5 in these tissues by sildenafil may be the basis for the enhanced platelet anti-aggregatory activity of nitric oxide observed in vitro, and the mild peripheral arterial-venous dilatation in vivo. None of these factors had a significant impact on sildenafil pharmacokinetics in patients with PAH.

Detection in biological fluids

The mean steady-state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. 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). Sildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes. The major circulating 200mg sildenafil citrate metabolite results from N-desmethylation of sildenafil, and is, itself, further metabolized. 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 patients with PAH, the average steady-state concentrations were 20% to 50% higher when compared to those of healthy volunteers.

Brand names

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. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. 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 citrate is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25% to 63%). When sildenafil citrate is taken with a high-fat meal, the rate of absorption is reduced, with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%. There was also a doubling of Cmin levels compared to healthy volunteers.

Storage Condition	Details	Temperature Range	Light Exposure	Humidity
Preferred Storage	Cool, dry place	15-30°C	Keep in original container	Avoid humidity
Keep away from light	Protect from direct sunlight	N/A	Yes	N/A
Out of reach of children	Safety precaution	N/A	N/A	N/A

Both findings suggest a lower clearance and/or a higher oral bioavailability of sildenafil in patients with PAH compared to healthy volunteers.

Condition	Description	Recommended Dosage	Notes
Erectile Dysfunction (ED)	Difficulty achieving or maintaining an erection	50 mg before activity	Can be adjusted based on response
Pulmonary Arterial Hypertension	High blood pressure in lungs	20 mg three times daily	Prescribed under medical supervision
Off-label uses	Other potential uses	Varies	Use under healthcare provider guidance

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).

Side Effect	Severity	Common Symptoms	Frequency
Headache	Mild to Moderate	Throbbing pain, sensation of pressure	Very common
Flushing	Mild	Skin redness, warmth	Common
Dyspepsia (Indigestion)	Mild	Burning sensation in stomach	Common
Visual disturbances	Mild to moderate	Blue tint, blurred vision	Less common
Priapism	Severe	Prolonged and painful erection	Rare

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.

Before taking this medicine

No patients died during the 16-week controlled study. After completing the 16-week controlled study, a patient originally randomized to sildenafil citrate remained on his/her dose of sildenafil citrate or, if originally randomized to placebo, was randomized to low-, medium-, or high-dose sildenafil citrate. After all patients completed 16 weeks of follow-up in the controlled study, the blind was broken and doses were adjusted as clinically indicated. Patients treated with sildenafil were followed for a median of 4.6 years (range 2 days to 8.6 years). Mortality during the long-term study, by originally assigned dose, is shown in Figure 6: During the study, there were 42 reported deaths with 37 of these deaths reported prior to a decision to titrate subjects to a lower dosage because of a finding of increased mortality with increasing sildenafil citrate doses.

Package and Label Display Panel

For the survival analysis which included 37 deaths, the hazard ratio for high dose compared to low dose was 3.9, p=0.007. Causes of death were typical of patients with PAH. Clinical studies of sildenafil citrate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Regional issues

There is no FDA guidance on the use of Sildenafil with respect to specific gender populations. There is no FDA guidance on the use of Sildenafil with respect to specific racial populations. No dose adjustment is required (including severe impairment CLcr < 30 mL/min). No dose adjustment for mild to moderate impairment is required. There is no FDA guidance on the use sildenafil 100mg lowest price of Sildenafil in women of reproductive potentials and males. 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.

Sildenafil is not recommended for children or minors.
Elderly patients may need lower doses due to sensitivity.
Use with caution if you have a history of stroke or unstable angina.
Combining sildenafil with other ED drugs increases side effects risks.
Be aware of counterfeit or substandard sildenafil products.
Always purchase medication from reputable pharmacies.
Consult a healthcare professional prior to initiating therapy.

Common Dosages of Sildenafil Citrate