Viagra and health: Beyond ED

In patients with PAH, however, the ratio

• Sildenafil 10mg can cause dizziness or vision changes in some users.
• Always check for drug interactions before taking sildenafil.
• It is important to stay hydrated when using sildenafil.
• The medication is not effective as an aphrodisiac without stimulation.
• Seek emergency help if you experience chest pain after use.

of the metabolite to sildenafil is higher. Both sildenafil and the active metabolite have

Understanding Tadalafil and Sildenafil

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 [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.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 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 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).Effects of Sildenafil on VisionAt 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.

How effective are vardenafil and sildenafil for erectile dysfunction?

An evaluation of visual function at doses up to 200 mg revealed no effects of sildenafil on visual acuity, intraocular pressure, or pupillometry.Pediatric use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil). However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information.12.3 PharmacokineticsAbsorption and DistributionSildenafil is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (25 to 63%). Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. When sildenafil 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%. The mean steady state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. terminal half-lives of about 4 hours.After either oral

or intravenous administration, sildenafil is excreted as

metabolites predominantly in the

• Men on sildenafil should avoid grapefruit or grapefruit juice.
• Sildenafil 10mg is less likely to cause side effects compared to higher doses.
• Regular exercise and healthy lifestyle can improve erectile function.
• Sildenafil has been in use for over two decades with proven safety.
• Patients should consult a healthcare provider if unsure about dosage.

feces (approximately 80% of

Other targets: Side effects

Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations.Metabolism and ExcretionSildenafil is cleared predominantly by the CYP3A (major route) and cytochrome P450 2C9 (CYP2C9, minor route) hepatic microsomal isoenzymes. The major circulating 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 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. the administered oral dose) and to a

5.8 Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell Disease

Sildenafil is also marketed as VIAGRA® for erectile dysfunction. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation. In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the sildenafil 25mg tablets systemic circulation.Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, greater than 80-fold for PDE1, greater than 700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE-5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility.

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Sildenafil is only about 10 times as potent for PDE5 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 [see Clinical Pharmacology (12.2)].In addition to pulmonary vascular smooth muscle and the corpus cavernosum, PDE5 is also found in other tissues including vascular and visceral smooth muscle and in platelets. The inhibition of PDE5 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.12.2 PharmacodynamicsEffects of Sildenafil on Hemodynamic MeasuresAdultsPatients on all sildenafil doses achieved a statistically significant reduction in mean pulmonary arterial pressure (mPAP) compared to those on placebo in a study with no background vasodilators [see SUPER-1 in Clinical Studies (14)]. Data on other hemodynamic measures for the sildenafil 20 mg three times a day and placebo dosing regimens is displayed in Table 2. The relationship between these effects and improvements in 6-minute walk distance is unknown.Effects of Sildenafil on Blood PressureSingle 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). lesser extent in the urine (approximately 13% of

How should I take sildenafil?

Clinical studies of sildenafil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from 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 [see Clinical Pharmacology (12.3)]. No dose adjustment for mild to moderate impairment is required. Severe impairment has not been studied [see Clinical Pharmacology (12.3)]. No dose adjustment is required (including severe impairment CLcr <30 mL/min) [see Clinical Pharmacology (12.3)].

Advantages Over Taking Both Pills Separately

10 OVERDOSAGE 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. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is not eliminated in the urine. 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. Sildenafil is also marketed as VIAGRA® for erectile dysfunction.Sildenafil citrate 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:Sildenafil citrate USP is a white or almost white slightly hygroscopic crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7.Sildenafil injection is supplied as a clear, colorless, sterile, ready to use solution in a single-dose vial containing 10 mg/12.5 mL of sildenafil. Each mL of solution contains 1.124 mg sildenafil citrate USP equivalent to 0.8 mg sildenafil, 50.5 mg dextrose and water for injection. the administered oral dose).Sildenafil

• Erectile dysfunction can be caused by various medical conditions; discuss treatment options with a doctor.
• The medication is generally well-tolerated but requires medical supervision.
• Side effects can include indigestion, muscle aches, or flushing.
• Avoid using sildenafil if you are pregnant or breastfeeding.
• Proper dosage and timing maximize the benefits of sildenafil 10mg.

Injection: The pharmacokinetic profile

of sildenafil has been

• The onset of action for sildenafil 10mg is usually within 30 minutes.
• It is important to follow prescribed intervals between doses.
• Sildenafil is not intended for recreational use.
• Consult your doctor if you experience prolonged erections.
• Women should avoid using sildenafil unless prescribed for pulmonary hypertension.

characterized following intravenous administration.

What is sildenafil (Viagra®)?

In a rat pre- and postnatal development study, the no-observed-adverse-effect dose was 30 mg/kg/day (equivalent to 5-times the RHD on a mg/m2 basis).8.2 LactationRisk SummaryLimited published data from a case report describe the presence of sildenafil and its active metabolite in human milk. There is insufficient information about the effects of sildenafil on the breastfed infant and no information on the effects of sildenafil on milk production. Limited clinical data during lactation preclude a clear determination of the risk of sildenafil to an infant during lactation.8.4 Pediatric UseThe safety and effectiveness of sildenafil have not been established in pediatric patients younger than 1 year of age.Pediatric use information is approved for Viatris Specialty LLC's, REVATIO (sildenafil). However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information.8.5 Geriatric UseClinical studies of sildenafil did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Contraindications for Tadalafil and Sildenafil?

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 [see Clinical Pharmacology (12.3)].8.6 Patients with Hepatic ImpairmentNo dose adjustment for mild to moderate impairment is required. Severe impairment has not been studied [see Clinical Pharmacology (12.3)].8.7 Patients with Renal ImpairmentNo dose adjustment is required (including severe impairment CLcr <30 mL/min) [see Clinical Pharmacology (12.3)]. Limited published data from a case report describe the presence of sildenafil and its active metabolite in human milk. Limited clinical data during lactation preclude a clear determination of the risk of sildenafil to an infant during lactation. The safety and effectiveness of sildenafil have not been established in pediatric patients younger than 1 year of age.