Drug Name

Viagra (Sildenafil)

Generic Name

Sildenafil (sil-DEN-a-fil)

Looks like

Sildenafil is available with a prescription under the brand name Viagra. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

• Viagra 25 mg-blue, film-coated rounded-diamond-shaped tablets
• Viagra 50 mg-blue, film-coated rounded-diamond-shaped tablets
• Viagra 100 mg-blue, film-coated rounded-diamond-shaped tablets

Dosage Form

Tablets

Route Of Administration

ORAL

Imprint Code

VGR25 / VGR50 / VGR100

Size

9mm / 11mm / 14mm

Alternatives

Impotence
Cialis, Levitra, Yohimbe, Muse, Yohimbine, Alprostadil

Drug Uses

Viagra is used to treat impotence in men. It increases the body's ability to achieve and maintain an erection during sexual stimulation.

Drug class

Viagra is a phosphodiesterase inhibitor. It works by helping the blood flow into the penis to achieve and maintain an erection.

Contains

Viagra (sildenafil citrate) is formulated as blue, film-coated rounded-diamond-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. In addition to the active ingredient, sildenafil citrate, each tablet contains the following inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, lactose, triacetin, and FD & C Blue #2 aluminum lake.

Chemical formula

Viagra is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).
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.

Mechanism of Action

The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO 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. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.
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, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is 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 human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle. The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo.

How Taken

Take sildenafil exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.
Take each dose with a full glass of water.
Sildenafil is usually taken when needed. It can be taken anywhere from 4 hours to one-half hour before sexual activity. Generally, it is taken 1 hour before sexual activity. The medication can help achieve an erection when sexual stimulation occurs. An erection will not occur just by taking a pill. Follow your doctor's instructions.
Taking sildenafil after eating a high-fat meal (such as a cheeseburger and french fries) may cause the medication to take a little longer to start working.
Do not take sildenafil more than once a day.
If you develop dizziness, nausea, or angina (pain, tightness, discomfort, numbness, or tingling in the chest, arms, neck, or jaw) during sexual activity, refrain from further sexual activity and notify your doctor.
Contact your doctor or seek emergency medical attention for any erection that lasts longer than 4 hours. A sustained erection can damage the penis.
Grapefruit and grapefruit juice may interact with sildenafil. The interaction could lead to potentially adverse effects. You should discuss the use of grapefruit and grapefruit juice with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.
Store this medication at room temperature away from moisture and heat.

Dosage and Administration

For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. However, Viagra may be taken anywhere from 4 hours to 0.5 hour before sexual activity. Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg. The maximum recommended dosing frequency is once per day.
Viagra was shown to potentiate the hypotensive effects of nitrates and its administration in patients who use nitric oxide donors or nitrates in any form is therefore contraindicated.

Usual Starting Dose

The recommended starting dose of Viagra is 50 mg approximately 1 hour before sexual activity.

Missed Dose

Viagra is used as needed, so you are not likely to miss a dose.

Overdose

Seek emergency medical attention if you think you have used too much of this medicine. Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center ( http://www.aapcc.org/findyour.htm ), or emergency room immediately.
Symptoms of a viagra overdose are not known, but are likely to include chest pain, dizziness, an irregular heartbeat, and swelling of the ankles or legs.

Storage

Store at 25C (77F); excursions permitted to 15-30C (59-86F).

How Supplied

Viagra (sildenafil citrate) is supplied as blue, film-coated, rounded-diamond-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration.

What is the most important information I should know about Viagra (Sildenafil)?

A small number of patients have lost eyesight in one eye after taking viagra. This type of vision loss is called non-arteritic anterior ischemic optic neuropathy (NAION). NAION causes a sudden loss of eyesight because blood flow is blocked to the optic nerve. It is not clear at this time if viagra causes NAION. NAION also happens in patients who do not take this medicine. People who have a higher chance for NAION include those who:

• have heart disease;
• are over 50 years old;
• have diabetes;
• have high blood pressure;
• have high cholesterol;
• smoke; or
• have certain eye problems.

Stop using viagra if you have any loss in your eyesight and seek medical help right away.
Do not take viagra if you are using a nitrate drug for chest pain or heart problems. Nitrates include nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, Minitran, Deponit, Transderm-Nitro, others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers").
Contact your doctor or seek emergency medical attention for any erection that lasts longer than 4 hours. A sustained erection can damage the penis.
Refrain from further sexual activity and notify your doctor it you develop dizziness, nausea, or angina (pain, tightness, discomfort, numbness, or tingling in the chest, arms, neck, or jaw) during sexual activity.
Do not take viagra more than once a day.

What should I discuss with my doctor before taking Viagra (Sildenafil)?

Before taking viagra, tell your doctor if you

• have had a heart attack, stroke, or life-threatening irregular heartbeats within the last six months;
• have a history of heart failure;
• have coronary artery disease;
• have angina;
• have high or low blood pressure;
• have liver problems;
• have kidney problems;
• have ever had blood problems, including sickle cell anemia or leukemia;
• have a bleeding disorder;
• have a stomach ulcer;
• have retinitis pigmentosa (an inherited condition of the eye);
• have a physical deformity of the penis such as Peyronie's disease;
• have a condition that could lead to prolonged and painful erections, such as a tumor of the bone marrow, sickle cell anemia, or leukemia; or
• are taking another medicine to treat impotence, such as alprostadil (Caverject, Muse, Edex) or yohimbine (Yocon, Yodoxin, others).

You may not be able to take viagra, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.
Although viagra is not indicated for use by women, it is in the FDA pregnancy category B. This means that viagra is not expected to be harmful to an unborn baby. viagra should not be taken by women.
It is not known whether viagra passes into breast milk. viagra should not be taken by women.
If you are over 65 years of age, you may be more likely to experience side effects from viagra. Your doctor may prescribe a lower dose of this medication.

Absorption

Viagra is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. When Viagra 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%.

Distribution

The mean steady state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. 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 Excretion

Sildenafil is cleared predominantly by the CYP3A4 (major route) and 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 PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% of the parent drug. 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.
After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the feces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose). Similar values for pharmacokinetic parameters were seen in normal volunteers and in the patient population, using a population pharmacokinetic approach.

Special Populations

Geriatric

Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, with free plasma concentrations approximately 40% greater than those seen in healthy younger volunteers (18-45 years).

Pediatric

Viagra is not indicated for use in newborns, children, or women.

Race

Pharmacokinetic data among various ethnic groups are not available.

Renal Insufficiency

In volunteers with mild (CLcr=50-80 mL/min) and moderate (CLcr=30-49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of Viagra (50 mg) were not altered. In volunteers with severe (CLcr=<30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in approximately doubling of AUC and Cmax compared to age-matched volunteers with no renal impairment.

Hepatic Impairment

In volunteers with hepatic cirrhosis (Child-Pugh 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.
Therefore, age >65, hepatic impairment and severe renal impairment are associated with increased plasma levels of sildenafil. A starting oral dose of 25 mg should be considered in those patients.

Possible side effects

Like all medicines, Viagra can cause some side effects. These effects are usually mild to moderate and usually don't last longer than a few hours. Some of these side effects are more likely to occur with higher doses. The most common side effects of Viagra are headache, flushing of the face, and upset stomach. Less common side effects that may occur are temporary changes in color vision (such as trouble telling the difference between blue and green objects or having a blue color tinge to them), eyes being more sensitive to light, or blurred vision.
In rare instances, men taking PDE5 inhibitors (oral erectile dysfunction medicines, including Viagra) reported a sudden decrease or loss of vision in one or both eyes. It is not possible to determine whether these events are related directly to these medicines, to other factors such as high blood pressure or diabetes, or to a combination of these. If you experience sudden decrease or loss of vision, stop taking PDE5 inhibitors, including Viagra, and call a doctor right away.
In rare instances, men have reported an erection that lasts many hours. You should call a doctor immediately if you ever have an erection that lasts more than 4 hours. If not treated right away, permanent damage to your penis could occur (see How Sex Affects the Body).
Heart attack, stroke, irregular heart beats, and death have been reported rarely in men taking Viagra. Most, but not all, of these men had heart problems before taking this medicine. It is not possible to determine whether these events were directly related to Viagra.
Viagra may cause other side effects besides those listed on this sheet. If you want more information or develop any side effects or symptoms you are concerned about, call your doctor.

What other drugs will affect Viagra (Sildenafil)?

Do not take sildenafil if you are using a nitrate drug for chest pain or heart problems. Nitrates include nitroglycerin (Nitrostat, Nitrolingual, Nitro-Dur, Nitro-Bid, Minitran, Deponit, Transderm-Nitro, others), isosorbide dinitrate (Dilatrate-SR, Isordil, Sorbitrate), and isosorbide mononitrate (Imdur, ISMO, Monoket). Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite ("poppers").
Before taking sildenafil, tell your doctor if you are taking any of the following medications:

• any other drug used to treat impotence, such as alprostadil (Caverject, Muse, Edex) or yohimbine (Yocon, Yodoxin, others);
• the antibiotic drugs clarithromycin (Biaxin), erythromycin (E-Mycin, Eryc, Ery-Tab, others), or troleandomycin (TAO);
• an antifungal medication such as itraconazole (Sporanox) or ketoconazole (Nizoral);
• the HIV medications amprenavir (Agenerase), delavirdine (Rescriptor), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), or saquinavir (Fortovase, Invirase);
• cimetidine (Tagamet, Tagamet HB);
• phenobarbital (Luminal);
• carbamazepine (Tegretol) or phenytoin (Dilantin); or
• rifampin (Rifadin, Rifamate) or rifabutin (Mycobutin).

You may not be able to take sildenafil, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medicines listed above.
Drugs other than those listed here may also interact with sildenafil or affect your condition. Talk to your doctor or pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

What should I avoid while taking Viagra (Sildenafil)?

Do not take any other drug used to treat impotence, such as alprostadil (Caverject, Muse, Edex) or yohimbine (Yocon, Yodoxin, others), without first talking to your doctor.
Grapefruit and grapefruit juice may interact with sildenafil. The interaction could lead to potentially adverse effects. You should discuss the use of grapefruit and grapefruit juice with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Contraindications

Consistent with its known effects on the nitric oxide/cGMP pathway Viagra was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is therefore contraindicated.
After patients have taken Viagra, it is unknown when nitrates, if necessary, can be safely administered. Based on the pharmacokinetic profile of a single 100 mg oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL). In the following patients: age >65, hepatic impairment (e.g., cirrhosis), severe renal impairment (e.g., creatinine clearance <30 mL/min), and concomitant use of potent cytochrome P450 3A4 inhibitors (erythromycin), plasma levels of sildenafil at 24 hours post dose have been found to be 3 to 8 times higher than those seen in healthy volunteers. Although plasma levels of sildenafil at 24 hours post dose are much lower than at peak concentration, it is unknown whether nitrates can be safely coadministered at this time point.
Viagra is contraindicated in patients with a known hypersensitivity to any component of the tablet.

Warnings

There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including Viagra, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.
Viagra has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.4/5.5 mmHg). While this normally would be expected to be of little consequence in most patients, prior to prescribing Viagra, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects, especially in combination with sexual activity.
Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators including Viagra - those with left ventricular outflow obstruction (e.g. aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure.
There is no controlled clinical data on the safety or efficacy of Viagra in the following groups; if prescribed, this should be done with caution.

• Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months;
• Patients with resting hypotension (BP <90/50) or hypertension (BP >170/110);
• Patients with cardiac failure or coronary artery disease causing unstable angina;
• Patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of Viagra. In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.
The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC). If Viagra is prescribed to patients taking ritonavir, caution should be used. Data from subjects exposed to high systemic levels of sildenafil are limited. Visual disturbances occurred more commonly at higher levels of sildenafil exposure. Decreased blood pressure, syncope, and prolonged erection were reported in some healthy volunteers exposed to high doses of sildenafil (200-800 mg). To decrease the chance of adverse events in patients taking ritonavir, a decrease in sildenafil dosage is recommended.

Precautions

Viagra has systemic vasodilatory properties and may augment the blood pressure lowering effect of other anti-hypertensive medications.
The safety of Viagra is unknown in patients with bleeding disorders and patients with active peptic ulceration.
Viagra should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
The safety and efficacy of combinations of Viagra with other treatments for erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.
In humans, Viagra has no effect on bleeding time when taken alone or with aspirin. In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor). The combination of heparin and Viagra had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans.

Information For Patients

Carcinogenesis/ Mutagenesis/ Impairment of Fertility

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. 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.
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 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.
There was no effect on sperm motility or morphology after single 100 mg oral doses of Viagra in healthy volunteers.

Pregnancy

Viagra is not indicated for use in newborns, children, or women.

Nursing Mothers

Viagra is not indicated for use in newborns, children, or women.

Pediatric Use

Viagra is not indicated for use in newborns, children, or women.

Geriatric Use

Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil. Since higher plasma levels may increase both the efficacy and incidence of adverse events, a starting dose of 25 mg should be considered.

FDA Alert

[Posted 10/18/2007]
FDA informed healthcare professionals of reports of sudden decreases or loss of hearing following the use of PDE5 inhibitors Viagra, Levitra, Cialis for the treatment of erectile dysfunction, and Revatio for the treatment of pulmonary arterial hypertension. In some cases, the sudden hearing loss was accompanied by tinnitus and dizziness. Medical follow-up on these reports was often limited which makes it difficult to determine if the loss of hearing was related to the use of one of the drugs, an underlying medical condition or other risk factors for hearing loss, a combination of these factors or other factors. The PRECAUTIONS and ADVERSE REACTIONS sections of the approved product labeling for Viagra, Levitra, and Cialis were revised. FDA is working with the manufacturer to revise the labeling for Revatio.

References

References and complaints