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Sildenafil causes mild and transient decreases in systemic blood pressure which, in the majority of cases, do not translate into clinical effects 11,12,13,14,15,16,8,9 .

After chronic dosing of 80 mg, three times a day to patients with systemic hypertension the mean change from baseline in systolic and diastolic blood pressure was a decrease of 9.4 mmHg and 9.1 mmHg respectively 11,12,13,14,15,16,8,9 . After chronic dosing of 80 mg, three times a day to patients with pulmonary arterial hypertension lesser effects in blood pressure reduction were observed (a reduction in both systolic and diastolic pressure of 2 mmHg) 11,12,13,14,15,16,8,9 . At the recommended dose of 20 mg three times a day no reductions in systolic or diastolic pressure were seen 11,12,13,14,15,16,8,9 .

Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG 11,12,13,14,15,16,8,9 .

After chronic dosing of 80 mg three times a day to patients with pulmonary arterial hypertension no clinically relevant effects on the ECG were reported either 11,12,13,14,15,16,8,9 .

In a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (> 70 % stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7 % and 6 % respectively compared to baseline 11,12,13,14,15,16,8,9 .

Mean pulmonary systolic blood pressure decreased by 9% 11,12,13,14,15,16,8,9 . Sildenafil showed no effect on cardiac output and did not impair blood flow through the stenosed coronary arteries 11,12,13,14,15,16,8,9 . Mild and transient differences in color discrimination (blue/green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose 11,12,13,14,15,16,8,9 .

The postulated mechanism for this change in color discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina 11,12,13,14,15,16,8,9 . Sildenafil has no effect on visual acuity or contrast sensitivity.

In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n = 9), sildenafil (single dose, 100 mg) demonstrated no significant changes in visual tests conducted (which included visual acuity, Amsler grid, color discrimination simulated traffic light, and the Humphrey perimeter and photostress test) 11,12,13,14,15,16,8,9 . Sildenafil is an oral therapy for erectile viagra pills no prescription dysfunction 5,12,13,16,8 .

with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis 5,12,13,16,8 .

The physiological mechanism responsible for the erection viagra pills no prescription of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation 5,12,13,16,8 .

Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood 5,12,13,16,8 . Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP 5,12,13,16,8 . Sildenafil has a peripheral site of action on erections 5,12,13,16,8 .

Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue 5,12,13,16,8 . When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP 5,12,13,16,8 . Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects 5,12,13,16,8 . Moreover, apart from the presence of PDE5 in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature 4,11,14,15,9 . Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation 4,11,14,15,9 . In patients with pulmonary arterial hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation 4,11,14,15,9 . Sildenafil is known to be quickly absorbed, with maximum plasma concentrations being observed within 30-120 minutes (with a median of 60 minutes) of oral administration in a fasting patient 11,12,13,14,15,16,8,9 .

Moreover, the mean absolute bioavailability observed for sildenafil is about 41% (from a range of 25-63%) 11,12,13,14,15,16,8,9 . In particular, after oral three times a day dosing of sildenafil, the AUC and Cmax increase in proportion with dose over the recommended dosage range of 25-100 mg 11,12,13,14,15,16,8,9 . When used in pulmonary arterial hypertension patients, however, the oral bioavailability of sildenafil after a dosing regimen of 80 mg three times a day, was on average 43% greater than compared to the lower doses 11,12,13,14,15,16,8,9 .

Finally, if sildenafil is administered orally with food, the rate of absorption is observed to be decreased with a mean delay in Tmax of about 60 minutes and a mean decrease in Cmax of approximately 29% 11,12,13,14,15,16,8,9 . Regardless, the extent of absorption is not observed to be significantly affected as the recorded AUC decreased by only about 11 % 11,12,13,14,15,16,8,9 . The mean steady-state volume of distribution documented for sildenafil is approximately 105 L - a value which suggests the medication undergoes distribution into the tissues 11,12,13,14,15,16,8,9 .

It is generally observed that sildenafil and its main circulating N-desmethyl metabolite are both estimated to be about 96% bound to plasma proteins 11,12,13,14,15,16,8,9 .

Nevertheless, it has been determined that protein binding for sildenafil is independent of total drug concentrations 11,12,13,14,15,16,8,9 . The metabolism of sildenafil is facilitated primarily by the CYP3A4 hepatic microsomal isoenzymes and to a minor extent, via the CYP2C9 hepatic isoenzymes 6,11,12,13,14,15,16,8,9 . The predominant circulating metabolite results from the N-demethylation of sildenafil 6,11,12,13,14,15,16,8,9 . This particular resultant metabolite possesses a phosphodiesterase selectivity that is similar to the parent sildenafil molecule and a corresponding in vitro potency for PDE5 that is approximately 50% that of the parent drug 6,11,12,13,14,15,16,8,9 .

Moreover, plasma concentrations of the metabolite are about 40% of those recorded for sildenafil, a percentage that accounts for about 20% of sildenafil’s pharmacologic effects 6,11,12,13,14,15,16,8,9 .

This primary N-desmethyl metabolite of sildenafil also undergoes further metabolism, with a terminal half-life of about 4 hours 6,11,12,13,14,15,16,8,9 . In patients with pulmonary arterial hypertension, plasma concentrations of the primary N-desmethyl metabolite are about 72% those of the original parent sildenafil molecule after a regimen of 20 mg three times a day - which is consequently responsible for about a 36% contribution to sildenafil’s overall pharmacological effects 6,11,12,13,14,15,16,8,9 . Hover over products below to view reaction partners.

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) 11,12,13,14,15,16,8,9 . The terminal phase half-life observed for sildenafil is approximately 3 to 5 hours 11,12,13,14,15,16,8,9 . The total body clearance documented for sildenafil is 41 L/h 11,12,13,14,15,16,8,9 . In single-dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased 11,12,13,14,15,16,8,9 .

Doses of 200 mg did not result in increased efficacy but the incidence of adverse reaction (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision) was increased 11,12,13,14,15,16,8,9 .

Due to the lack of data on the effect of sildenafil indicated for the treatment of pulmonary arterial hypertension (PAH) in pregnant women, sildenafil is not recommended for women of childbearing potential unless also using appropriate contraceptive measures 11,14,15,9 .

The safety and efficacy of sildenafil indicated for treating PAH in a woman during labor and delivery have not been studied 11,14,15,9 .

Caution should ultimately be exercised when sildenafil is administered to nursing women as it is not known if sildenafil or its metabolites are excreted in human breast milk 11,14,15,9 .

The safety and efficacy of sildenafil for the treatment of PAH in children below 1 year of age has not been established as no data is available 15 . Clinical experience with the elderly population in the use of sildenafil for the treatment of PAH has been varied. Some reports suggest that there are no identified differences in responses between elderly and younger patients 11 while others have documented that clinical efficacy as measured by 6-minute walk distance could be less in elderly patients 9 .

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 11 .

Conversely, when sildenafil was used to treat erectile dysfunction in healthy elderly volunteers (65 years or over), a reduced clearance of sildenafil was observed 12,8 . This reduction resulted in about 90% higher plasma concentrations of sildenafil and the active N-desmethyl metabolite compared to those seen in healthy younger volunteers (18-45 years) 12,8 .

Due to age-differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40% 12,8 .

Sildenafil was not carcinogenic when administered to rats for 24 months at a dose resulting in total systemic drug exposure (AUCs) for unbound sildenafil and its major metabolite of 29- and 42- times, for male and female rats, respectively, the exposures observed in human males given the Maximum Recommended Human Dose (MRHD) of 100 mg 11,12,13,14,15,16,8,9 . Sildenafil was not carcinogenic when administered to mice for 18-21 months at dosages up to the Maximum Tolerated Dose (MTD) of 10 mg/kg/day, approximately 0.6 times the MRHD on a mg/m2 basis 11,12,13,14,15,16,8,9 .

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 11,12,13,14,15,16,8,9 . There was no impairment of fertility in rats given sildenafil up to 60 mg/kg/day for 36 days to females and 102 days to males, a dose producing an AUC value of more than 25 times the human male AUC 11,12,13,14,15,16,8,9 .

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What is the most important information I should know about oral sildenafil?

Some medicines can cause unwanted or dangerous effects when used with sildenafil.

Tell your doctor about all your current medicines, especially riociguat (Adempas). Do not take sildenafil if you are also using a nitrate drug for chest pain or heart problems, including nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, and some recreational drugs such as "poppers".

Taking sildenafil with a nitrate medicine can cause a sudden and serious decrease in blood pressure.

Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis. Stop viagra pills no prescription using sildenafil and get emergency medical help if you have sudden vision loss. Sildenafil relaxes muscles of the blood vessels and increases blood flow to particular areas of the body. Sildenafil under the name Viagra is used to treat erectile dysfunction (impotence) in men. Another brand of sildenafil is Revatio , which is used to treat pulmonary arterial hypertension and improve exercise capacity in men and women.

Do not take Viagra while also taking Revatio, unless your doctor tells you to.

Sildenafil may also be used for purposes not listed in this medication guide. What should I discuss with my healthcare provider before taking oral sildenafil?

You should not use sildenafil if you are allergic to it, or: if you take other medicines to treat pulmonary arterial hypertension, such as riociguat (Adempas).

Do not take sildenafil if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin, isosorbide dinitrate, and viagra pills in walgreens isosorbide mononitrate.

Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers"). Taking sildenafil with a nitrate medicine can cause a sudden and serious decrease in blood pressure.

Tell your doctor if you have ever had: heart problems (chest pain, a heart rhythm disorder, heart attack); high or low blood pressure; blood circulation problems; retinitis pigmentosa (an inherited condition of the eye); blindness in one or both eyes; bleeding problems; a stomach ulcer; pulmonary veno-occlusive disease (PVOD); liver or kidney disease; a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia; a physical deformity of the penis (such as Peyronie's disease); or if you have been told you should not have sexual intercourse for health reasons. Sildenafil can decrease blood flow to the optic nerve of the eye, causing sudden vision loss. This has occurred in a small number of people taking sildenafil, most of whom also had heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoked or were over 50 years old. It is not clear whether sildenafil is the actual cause of vision loss.

It is not known whether this medicine will harm an unborn baby. However, having pulmonary arterial hypertension (PAH) during pregnancy may cause complications such as heart failure, stroke, or medical problems in both mother and baby.

The benefit of treating PAH with Revatio may outweigh any risks to the baby.

It may not be safe to breast-feed while using this medicine.

Do not give this medication to anyone under 18 years old without medical advice. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Revatio is usually taken three times each day, about 4 to 6 hours apart.

Viagra is usually taken only when needed, 30 minutes to 1 hour before sexual activity.

You may take it up to 4 hours before sexual activity. Shake the oral suspension (liquid) before you measure a dose. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Viagra can help you have an erection when sexual stimulation occurs.

During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of sildenafil.

Store at room temperature away from moisture and heat. Since Viagra is used as needed, you are not likely to miss a dose. If you miss a dose of Revatio , take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Drinking alcohol with this medicine can cause side effects.

Grapefruit may interact with sildenafil and lead to unwanted side effects.

Avoid using any other medicines to treat impotence, such as alprostadil or yohimbine, without first talking to your doctor.

What are the possible side effects of oral sildenafil?

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop taking sildenafil and get emergency medical help if you have: heart attack symptoms --chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating; vision changes or sudden vision loss; or erection is painful or lasts longer than 4 hours (prolonged erection can damage the penis). Call your doctor at once if you have: severe shortness of breath, cough with foamy mucus; ringing in your ears, or sudden hearing loss; irregular heartbeat; swelling in your hands, ankles, or feet; a seizure; or (convulsions); or a light-headed feeling, like you might pass out.

Common side effects may include: flushing (warmth, redness, or tingly feeling); headache, dizziness; abnormal vision (blurred vision, changes in color vision) runny or stuffy nose, nosebleeds; sleep problems (insomnia); muscle pain, back pain; or upset stomach.

This is not a complete list of viagra pills no prescription side effects and others may occur. Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088. Do not take sildenafil with similar medications such as avanafil (Stendra), tadalafil (Cialis) or vardenafil (Levitra).

Tell your doctor about all other medications you use for

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Other drugs may affect sildenafil, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Your pharmacist can provide more information about sildenafil. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only fda approved generic viagra for the indication prescribed. Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise.

Multum's drug information does not endorse drugs, diagnose patients or recommend therapy.

Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is generic viagra soft tabs 100mg safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects.

If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.