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What is Generic viagra jeaeai?
viagra jeaeai® was originally patented by Pfizer and brought to the US market in 1998.
It is FDA-approved to treat erectile dysfunction (ED).
After the patent expired, the FDA gave permission to other drug companies to market a generic version of viagra jeaeai®.
The FDA requires generic drugs to be bioequivalent to the brand name version.
This means that they act the same way in the body and are expected to produce the same effects as the original brand name drug.
Generic drugs are generally much cheaper than the original brand name drug, and most drugs prescribed in the US are generic.
What is Sildenafil Citrate?
Sildenafil citrate is the chemical name of the active ingredient in viagra jeaeai®.
Sildenafil citrate is also sold in 20 mg tablets as the generic version of a drug called Revatio®, which is FDA approved for treating pulmonary hypertension.
Roman-affiliated physicians have the discretion to prescribe 20 mg sildenafil tablets for ED in doses ranging between 20 mg and 100 mg if they believe that it is an appropriate course of treatment for a particular patient.
Sildenafil 20 mg tablets for ED is an off-label usage of the medication.
It is up to the medical judgment of the doctor to decide if off-label treatment is appropriate for a patient based on his unique medical history, symptoms, and preferences.
The Roman Pharmacy Network is able to fill prescriptions for sildenafil 20 mg tablets that are issued by a Roman-affiliated physician.
Does Roman Offer Genuine viagra jeaeai?
Roman offers genuine, branded viagra jeaeai® and generic viagra jeaeai® to treat erectile dysfunction (ED).
Roman also offers sildenafil in 20 mg tablets, which can be prescribed by doctors off-label to treat ED in doses ranging between 20 mg and 100 mg if they find it medically appropriate to do so.
How Does viagra jeaeai Work?
In order to understand how viagra jeaeai® works to treat ED, it’s important to first understand the basics of how erections work.
Erotic stimulation (by physical touch, erotic thoughts, smells, etc) causes the local tissues to release nitric oxide (NO), which increases the amount of a chemical called cyclic guanosine monophosphate (cGMP).
At the same time veins that drain blood from the penis get compressed causing the increased blood to be trapped in the penis causing an erection.
An enzyme called phosphodiesterase-5 breaks down cGMP leading the penis to return to its flaccid state.
PDE5 inhibitors (PDE5i), like viagra jeaeai®, block this enzyme, leading to higher levels of cGMP and improving the ability to obtain and maintain an erection.
How Should I Take viagra jeaeai?
viagra jeaeai® should be taken 30–60 minutes before sex.
It’s important to take it without a meal because fat in a meal can decrease and delay its absorption, which can lower viagra jeaeai’s effectiveness.
Even though the instructions are to take it 30–60 minutes before sex, viagra jeaeai® lasts in the body for up to 6–8 hours.
How Long Does viagra jeaeai Take to Work?
viagra jeaeai® is a short acting medication with a rapid onset.
It should be taken 30–60 minutes before sex, and it reaches peak blood levels in 60 minutes on average.
Fat in a meal can delay the effects of viagra jeaeai® and also decrease the amount that is absorbed.
Remember that viagra jeaeai® will not give you a spontaneous erection without sexual stimulation.
How Long Does viagra jeaeai Last?
viagra jeaeai® is a short acting drug with an average half-life of 4–5 hours, which means that half the medicine is gone from the body after 4–5 hours in healthy people.
The time that it takes to eliminate viagra jeaeai® may be prolonged in older people and people with liver or kidney disease and the drug may work longer in these people.
Can viagra jeaeai Have Permanent Effects?
viagra jeaeai does not have permanent effects on the body once it is broken down.
It is only effective for as long as it is in the body.
Some people may find they need more medication after taking ED medication for a long time or it may not work as well as it used to.
However, this is not because the medicine is having permanent effects.
This happens because erectile function normally decreases with age.
In some cases, erectile function may also worsen due to progression of the underlying disease that is causing ED (e.
What Should I Tell My Doctor.
Tell your doctor if you have any problems with your heart, liver, kidneys, vision disorders, bleeding disorders, or penile deformities.
Tell your doctor about all prescription medications, over the counter medications, and dietary supplements you are taking.
For more safety information, please see the important safety information below.
Common Side Effects of viagra jeaeai.
The most common side effects of viagra jeaeai® include headaches, facial flushing, stuffy nose, and upset stomach.
Serious side effects that are rare include an erection that will not resolve even after 3–4 hours (priapism), hearing loss, which can be sudden, and vision loss in one or both eyes.
For more information about side effects, see viagra jeaeai® side effects below.
What Happens if I Overdose?
Taking more than the recommended amount of viagra jeaeai® or sildenafil citrate greatly increases your risk of side effects, including severe ones that can be dangerous, such as severe low blood pressure or an erection that won’t go away even after 4 or more hours (priapism).
Never take more than the amount prescribed to you by your doctor.
If you have any severe side effects after taking more than the recommended amount, or even after taking the amount of medicine prescribed to you, seek out emergency medical attention immediately.
Is Buying viagra jeaeai Online Safe?
Buying medication online can have risks when the source is not reputable.
One study showed that 77% of viagra jeaeai sold online was counterfeit.
Counterfeit PDE5i can have variable amounts of the active drug ranging from 0%–200+% of the drug.
In cases where the active ingredient is present in lower amounts than expected, this can mean lack of effectiveness even though the same dose of active drug may work well in a given individual.
In cases where much more active drug than listed is included, there is a higher potential for side effects, including dangerous ones like extremely low blood pressure or an erection that won’t go away even after 4 or more hours (priapism).
It is also common for counterfeit drugs to contain harmful ingredients like talcum powder, commercial paint, and printer ink.
With Roman, you can always be sure you are getting genuine medication with active ingredients in the correct amount without harmful additives.
Roman drugs are manufactured by pharmaceutical companies that are regulated by the FDA.
In fact you will likely find many of the same manufacturers we use in your local pharmacy.
With Roman, you never need to worry about what’s actually in the pills you are taking.
What Should You Know Before Taking viagra jeaeai.
Who should not take viagra jeaeai® or generic viagra jeaeai®?
Do not take viagra jeaeai® or generic viagra jeaeai® if you: take medicines called nitrates (such as nitroglycerin) use street drugs called “poppers” such as amyl nitrate or amyl nitrite, and butyl nitrate take any medicines called guanylate cyclase stimulators such as riociguat (Adempas) are allergic to sildenafil, as contained in viagra jeaeai® and Revatio, or any of the ingredients in viagra jeaeai®.
See the end of this leaflet for a complete list of ingredients in viagra jeaeai®.
What should I tell my healthcare provider before taking viagra jeaeai® or generic viagra jeaeai®?
To make sure viagra jeaeai® is safe for you, tell your healthcare provider if you have any of the following before you take viagra jeaeai® or generic viagra jeaeai®l: Have or have had heart problems such as a heart attack,irregular heartbeat, angina, chest pain, narrowing of the aortic valve, or heart failure Have had heart surgery within the last 6 months Have pulmonary hypertension Have had a stroke Have low blood pressure, or high blood pressure that is not controlled Have a deformed penis shape Have had an erection that lasted for more than 4 hours Have problems with your blood cells such as sickle cell anemia, multiple myeloma, or leukemia Have retinitis pigmentosa, a rare genetic (runs in families) eye disease Have ever had severe vision loss, including an eye problem called NAION Have bleeding problems Have or have had stomach or intestinal ulcers Have liver problems Have kidney problems or are having kidney dialysis Have any other medical conditions.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
viagra jeaeai® and generic viagra jeaeai® may affect the way other medicines work, and other medicines may affect the way viagra jeaeai® and generic viagra jeaeai® works, causing side effects.
Tell your healthcare provider if you take any of the following because these drugs interact with viagra jeaeai® and generic viagra jeaeai®: Medicines called nitrates Medicines called guanylate cyclase stimulators such as Adempas® (riociguat) Medicines called alpha-blockers such as Hytrin® (terazosin HCl), Flomax® (tamsulosin HCl), Cardura® (doxazosin mesylate), Minipress® (prazosin HCl), Uroxatral® (alfuzosin HCl), Jalyn® (dutasteride and tamsulosin HCl), or Rapaflo® (silodosin).
Alpha-blockers are sometimes prescribed for prostate problems or high blood pressure.
In some patients, the use of viagra jeaeai® or generic viagra jeaeai® with alpha-blockers can lead to a drop in blood pressure or to fainting Medicines called HIV protease inhibitors, such as ritonavir (Norvir®), indinavir sulfate (Crixivan®), saquinavir (Fortovase® or Invirase®), or atazanavir sulfate (Reyataz®) Oral antifungal medicines, such as ketoconazole (Nizoral®) and itraconazole (Sporanox®) Antibiotics, such as clarithromycin (Biaxin®), telithromycin (Ketek®), or erythromycin Other medicines that treat high blood pressure Other medicines or treatments for ED viagra jeaeai® and generic viagra jeaeai® contain sildenafil, which is the same medicine found in another drug called Revatio®.
Revatio® is used to treat a rare disease called pulmonary arterial hypertension (PAH).
viagra jeaeai® and generic viagra jeaeai® should not be used with Revatio® or with other PAH treatments containing sildenafil or any other PDE5 inhibitors (such as Adcirca [tadalafil]) Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.
Know the medicines you take.
Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.
What are the possible side effects of viagra jeaeai® and generic viagra jeaeai®?
viagra jeaeai® and generic viagra jeaeai® can cause serious side effects.
Rarely reported side effects include: an erection that will not go away (priapism).
If you have an erection that lasts more than 4 hours, get medical help right away.
If it is not treated right away, priapism can permanently damage your penis.
Sudden vision loss in one or both eyes can be a sign of a serious eye problem called non-arteritic anterior ischemic optic neuropathy (NAION).
It is uncertain whether PDE5 inhibitors directly cause the vision loss.
Stop taking viagra jeaeai® and call your healthcare provider right away if you have sudden vision loss in one or both eyes.
Some people may also have ringing in their ears (tinnitus) or dizziness.
If you have these symptoms, stop taking viagra jeaeai® or generic viagra jeaeai® and contact a doctor right away.
The most common side effects of viagra jeaeai® and generic viagra jeaeai® are: headache flushing upset stomach abnormal vision, such as changes in color vision (such as having a blue color tinge) and blurred vision stuffy or runny nose back pain muscle pain nausea dizziness Rash.
In addition, heart attack, stroke, irregular heartbeats and death have happened rarely in men taking viagra jeaeai®.
Most, but not all, of these men had heart problems before taking viagra jeaeai®.
It is not known if viagra jeaeai® caused these problems.
Tell your healthcare provider if you have any side effect that bothers you or does not go away.
These are not all the possible side effects of viagra jeaeai® and generic viagra jeaeai®.
For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088.
Find Lowest Prices on.
viagra jeaeai® (sildenafil citrate) Tablets.
viagra jeaeai (sildenafil citrate), an oral therapy for erectile dysfunction, 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[4,3d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate and has the following structural formula: Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.
viagra jeaeai 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.
viagra jeaeai is indicated for the treatment of erectile dysfunction.
For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity.
However, viagra jeaeai may be taken anywhere from 30 minutes to 4 hours before sexual activity.
The maximum recommended dosing frequency is once per day.
Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg.
viagra jeaeai may be taken with or without food.
Dosage Adjustments In Specific Situations.
viagra jeaeai was shown to potentiate the hypotensive effects of nitrates and its administration in patients who use nitric oxide donors such as organic nitrates or organic nitrites in any form is therefore contraindicated [see CONTRAINDICATIONS , DRUG INTERACTIONS , and CLINICAL PHARMACOLOGY ].
When viagra jeaeai is co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating viagra jeaeai treatment and viagra jeaeai should be initiated at 25 mg [see WARNINGS AND PRECAUTIONS , DRUG INTERACTIONS , and CLINICAL PHARMACOLOGY ].
Dosage Adjustments Due To Drug Interactions.
The recommended dose for ritonavir-treated patients is 25 mg prior to sexual activity and the recommended maximum dose is 25 mg within a 48 hour period because concomitant administration increased the blood levels of sildenafil by 11-fold [see WARNINGS AND PRECAUTIONS , DRUG INTERACTIONS , and CLINICAL PHARMACOLOGY ].
Consider a starting dose of 25 mg in patients treated with strong CYP3A4 inhibitors (e.
Clinical data have shown that co-administration with saquinavir or erythromycin increased plasma levels of sildenafil by about 3 fold [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY ].
Dosage Adjustments In Special Populations.
Consider a starting dose of 25 mg in patients > 65 years, patients with hepatic impairment (e.
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature ].
Distributed by: Pfizer Labs, Division of Pfizer Inc.
SL >Erectile Dysfunction (ED) Causes and Treatment See Slideshow.
The following are discussed in more detail in other sections of the labeling: Cardiovascular [see WARNINGS AND PRECAUTIONS ] Prolonged Erection and Priapism [see WARNINGS AND PRECAUTIONS ] Effects on the Eye [see WARNINGS AND PRECAUTIONS ] Hearing Loss [see WARNINGS AND PRECAUTIONS ] Hypotension when Co-administered with Alpha-blockers or Anti-hypertensives [see WARNINGS AND PRECAUTIONS ] Adverse Reactions with the Concomitant Use of Ritonavir [see WARNINGS AND PRECAUTIONS ] Combination with other PDE5 Inhibitors or Other Erectile Dysfunction Therapies [see WARNINGS AND PRECAUTIONS ] Effects on Bleeding [see WARNINGS AND PRECAUTIONS ] Counseling Patients About Sexually Transmitted Diseases [see WARNINGS AND PRECAUTIONS ] The most common adverse reactions reported in clinical trials ( > 2%) are headache, flushing, dyspepsia, abnormal vision, nasal congestion, back pain, myalgia, nausea, dizziness, and rash.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
viagra jeaeai was administered to over 3700 patients (aged 19-87 years) during pre-marketing clinical trials worldwide.
Over 550 patients were treated for longer than one year.
In placebo-controlled clinical studies, the discontinuation rate due to adverse reactions for viagra jeaeai (2.
In fixed-dose studies, the incidence of some adverse reactions increased with dose.
The type of adverse reactions in flexible-dose studies, which reflect the recommended dosage regimen, was similar to that for fixed-dose studies.
At doses above the recommended dose range, adverse reactions were similar to those detailed in Table 1 below but generally were reported more frequently.
Table 1: Adverse Reactions Reported by ? 2% of Patients Treated with viagra jeaeai and More Frequent than Placebo in Fixed-Dose Phase II/III Studies Adverse Reaction 25 mg (n=312) 100 mg (n=506) Placebo (n=607) Headache 16% 21% 28% 7% Flushing 10% 19% 18% 2% Dyspepsia 3% 9% 17% 2% Abnormal vision† 1% 2% 11% 1% Nasal congestion 4% 4% 9% 2% Back pain 3% 4% 4% 2% Myalgia 2% 2% 4% 1% Nausea 2% 3% 3% 1% Dizziness 3% 4% 3% 2% Rash 1% 2% 3% 1% †Abnormal Vision: Mild to moderate in severity and transient, predominantly color tinge to vision, but also increased sensitivity to light, or blurred vision.
When viagra jeaeai was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials of two to twenty-six weeks duration, patients took viagra jeaeai at least once weekly, and the following adverse reactions were reported: Table 2: Adverse Reactions Reported by ? 2% of Patients Treated with viagra jeaeai and More Frequent than Placebo in Flexible-Dose Phase II/III Studies Adverse Reaction viagra jeaeai N=734 PLACEBO N=725 Headache 16% 4% Flushing 10% 1% Dyspepsia 7% 2% Nasal Congestion 4% 2% Abnormal Vision† 3% 0% Back pain 2% 2% Dizziness 2% 1% Rash 2% 1% †Abnormal Vision: Mild and transient, predominantly color tinge to vision, but also increased sensitivity to light or blurred vision.
In these studies, only one patient discontinued due to abnormal vision.
The following events occurred in.
Administration of viagra jeaeai with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated.
Consistent with its known effects on the nitric oxide/cGMP pathway, viagra jeaeai was shown to potentiate the hypotensive effects of nitrates [see DOSAGE AND ADMINISTRATION , CONTRAINDICATIONS , CLINICAL PHARMACOLOGY ].
Use caution when co-administering alpha-blockers with viagra jeaeai because of potential additive blood pressure-lowering effects.
When viagra jeaeai is co-administered with an alpha-blocker, patients should be stable on alpha-blocker therapy prior to initiating viagra jeaeai treatment and viagra jeaeai should be initiated at the lowest dose [see DOSAGE AND ADMINISTRATION , WARNINGS AND PRECAUTIONS , CLINICAL PHARMACOLOGY ].
When viagra jeaeai 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic [see WARNINGS AND PRECAUTIONS , CLINICAL PHARMACOLOGY ].
Ritonavir And Other CYP3A4 Inhibitors.
Co-administration of ritonavir, a strong CYP3A4 inhibitor, greatly increased the systemic exposure of sildenafil (11-fold increase in AUC).
It is therefore recommended not to exceed a maximum single dose of 25 mg of viagra jeaeai in a 48 hour period [see DOSAGE AND ADMINISTRATION , WARNINGS AND PRECAUTIONS , CLINICAL PHARMACOLOGY ].
Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in a 160% and 182% increases in sildenafil Cmax and AUC, respectively.
Co-administration of saquinavir, a strong CYP3A4 inhibitor, resulted in 140% and 210% increases in sildenafil Cmax and AUC, respectively.
Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole could be expected to have greater effects than seen with saquinavir.
A starting dose of 25 mg of viagra jeaeai should be considered in patients taking erythromycin or strong CYP3A4 inhibitors (such as saquinavir, ketoconazole, itraconazole) [see DOSAGE AND ADMINISTRATION , CLINICAL PHARMACOLOGY ].
In a drug-drug interaction study sildenafil 50 mg given with alcohol 0.
Included as part of the PRECAUTIONS section.
There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease.
Therefore, treatments for erectile dysfunction, including viagra jeaeai, should not be generally used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status.
The evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment.
viagra jeaeai has systemic vasodilatory properties that resulted in transient decreases in supine blood pressure in healthy volunteers (mean maximum decrease of 8.
While this normally would be expected to be of little consequence in most patients, prior to prescribing viagra jeaeai, 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.
Use with caution in patients with the following underlying conditions which can be particularly sensitive to the actions of vasodilators including viagra jeaeai – those with left ventricular outflow obstruction (e.
There are no controlled clinical data on the safety or efficacy of viagra jeaeai 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 170/110 mmHg); Patients with cardiac failure or coronary artery disease causing unstable angina.
Prolonged Erection And Priapism.
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 jeaeai.
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.
viagra jeaeai 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).
However, there are no controlled clinical data on the safety or efficacy of viagra jeaeai in patients with sickle cell or related anemias.
Effects On The Eye.
Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including viagra jeaeai, and seek medical attention in the event of a sudden loss of vision in one or both eyes.
Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision including permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors.
Based on published literature, the annual incidence of NAION is 2.
An observational study evaluated whether recent use of PDE5 inhibitors, as a class, was associated with acute onset of NAION.
The results suggest an approximate 2 fold increase in the risk of NAION within 5 half-lives of PDE5 inhibitor use.
From this information, it is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see ADVERSE REACTIONS ].
Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors.
Individuals who have already experienced NAION are at increased risk of NAION recurrence.
Therefore, PDE5 inhibitors, including viagra jeaeai, should be used with caution in these patients and only when the anticipated benefits outweigh the risks.
Individuals with “crowded” optic disc are also considered at greater risk for NAION compared to the general population, however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including viagra jeaeai, for this uncommon condition.
There are no controlled clinical data on the safety or efficacy of viagra jeaeai in patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases); if prescribed, this should be done with caution.
Physicians should advise patients to stop taking PDE5 inhibitors, including viagra jeaeai, and seek prompt medical attention in the event of sudden decrease or loss of hearing.
These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including viagra jeaeai.
It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see ADVERSE REACTIONS ].
Hypotension When Co-administered With Alpha-blockers Or Anti-hypertensives.
Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers.
PDE5 inhibitors, including viagra jeaeai, and alpha-adrenergic blocking agents are both vasodilators with blood pressure lowering effects.
When vasodilators are used in combination, an additive effect on blood pressure may occur.
In some patients, concomitant use of these two drug classes can lower blood pressure significantly [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY ] leading to symptomatic hypotension (e.
Consideration should be given to the following: Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors.
Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor.
In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest dose [see DOSAGE AND ADMINISTRATION ].
In those patients already taking an optimized dose of a PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose.
Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure when taking a PDE5 inhibitor.
Safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other variables, including intravascular volume depletion and other anti-hypertensive drugs.
viagra jeaeai has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications.
In a separate drug interaction study, when amlodipine, 5 mg or 10 mg, and viagra jeaeai, 100 mg were orally administered concomitantly to hypertensive patients mean additional blood pressure reduction of 8 mmHg systolic and 7 mmHg diastolic were noted [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY ].
Adverse Reactions With The Concomitant Use Of Ritonavir.
The concomitant administration of the protease inhibitor ritonavir substantially increases serum concentrations of sildenafil (11-fold increase in AUC).
If viagra jeaeai is prescribed to patients taking ritonavir, caution should be used.
Data from subjects exposed to high systemic levels of sildenafil are limited.
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 reactions in patients taking ritonavir, a decrease in sildenafil dosage is recommended [see DOSAGE AND ADMINISTRATION , DRUG INTERACTIONS , and CLINICAL PHARMACOLOGY ].
Combination With Other PDE5 Inhibitors Or Other Erectile Dysfunction Therapies.
The safety and efficacy of combinations of viagra jeaeai with other PDE5 Inhibitors, including REVATIO or other pulmonary arterial hypertension (PAH) treatments containing sildenafil, or other treatments for erectile dysfunction have not been studied.
Such combinations may further lower blood pressure.
Therefore, the use of such combinations is not recommended.
There have been postmarketing reports of bleeding events in patients who have taken viagra jeaeai.
A causal relationship between viagra jeaeai and these events has not been established.
In humans, viagra jeaeai has no effect on bleeding time when taken alone or with aspirin.
However, in vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside (a nitric oxide donor).
In addition, the combination of heparin and viagra jeaeai had an additive effect on bleeding time in the anesthetized rabbit, but this interaction has not been studied in humans.
The safety of viagra jeaeai is unknown in patients with bleeding disorders and patients with active peptic ulceration.
Counseling Patients About Sexually Transmitted Diseases.
The use of viagra jeaeai offers no protection against sexually transmitted diseases.
Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered.
See FDA-approved patient labeling (PATIENT INFORMATION) Physicians should discuss with patients the contraindication of viagra jeaeai with regular and/or intermittent use of nitric oxide donors, such as organic nitrates or organic nitrites in any form [see CONTRAINDICATIONS ].
Guanylate Cyclase (GC) Stimulators.
Physicians should discuss with patients the contraindication of viagra jeaeai with use of guanylate cyclase stimulators such as riociguat [see CONTRAINDICATIONS ].
Concomitant Use with Drugs Which Lower Blood Pressure.
Physicians should advise patients of the potential for viagra jeaeai to augment the blood pressure lowering effect of alpha-blockers and anti-hypertensive medications.
Concomitant administration of viagra jeaeai and an alpha-blocker may lead to symptomatic hypotension in some patients.
Therefore, when viagra jeaeai is co-administered with alpha-blockers, patients should be stable on alpha-blocker therapy prior to initiating viagra jeaeai treatment and viagra jeaeai should be initiated at the lowest dose [see WARNINGS AND PRECAUTIONS ].
Physicians should discuss with patients the potential cardiac risk of sexual activity in patients with preexisting cardiovascular risk factors.
Patients who experience symptoms (e.
Sudden Loss of Vision.
Physicians should advise patients to stop use of all PDE5 inhibitors, including viagra jeaeai, and seek medical attention in the event of a sudden loss of vision in one or both eyes.
Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including possible permanent loss of vision, that has been reported rarely post-marketing in temporal association with the use of all PDE5 inhibitors.
It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors.
Physicians should discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye.
Physicians should also discuss with patients the increased risk of NAION among the general population in patients with a “crowded” optic disc, although evidence is insufficient to support screening of prospective users of PDE5 inhibitor, including viagra jeaeai, for this uncommon condition [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS ].
Physicians should advise patients to stop taking PDE5 inhibitors, including viagra jeaeai, and seek prompt medical attention in the event of sudden decrease or loss of hearing.
These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including viagra jeaeai.
It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS ].
Physicians should warn patients that prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) have been reported infrequently since market approval of viagra jeaeai.
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 may result [see WARNINGS AND PRECAUTIONS ].
Avoid Use with other PDE5 Inhibitors.
Physicians should inform patients not to take viagra jeaeai with other PDE5 inhibitors including REVATIO or other pulmonary arterial hypertension (PAH) treatments containing sildenafil.
Sildenafil is also marketed as REVATIO for the treatment of PAH.
The safety and efficacy of viagra jeaeai with other PDE5 inhibitors, including REVATIO, have not been studied [see WARNINGS AND PRECAUTIONS ].
The use of viagra jeaeai offers no protection against sexually transmitted diseases.
Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including the Human Immunodeficiency Virus (HIV), may be considered [see WARNINGS AND PRECAUTIONS ].
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.
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.
Use In Specific Populations.
viagra jeaeai is not indicated for use in women.
There are no adequate and well-controlled studies of sildenafil in pregnant women.
Based on animal data, viagra jeaeai is not predicted to increase the risk of adverse developmental outcomes in humans.
No evidence of teratogenicity, embryotoxicity or fetotoxicity was observed in rats and rabbits which received up to 200 mg/kg/day during organogenesis.
These doses represent, respectively, about 20 and 40 times the Maximum Recommended Human Dose (MRHD) on a mg/m? basis in a 50 kg subject.
In the rat pre-and postnatal development study, the no observed adverse effect dose was 30 mg/kg/day given for 36 days.
In the nonpregnant rat the AUC at this dose was about 20 times human AUC.
viagra jeaeai is not indicated for use in pediatric patients.
Safety and effectiveness have not been established in pediatric patients.
Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy young volunteers (18-45 years) [see CLINICAL PHARMACOLOGY ].
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 [see CLINICAL PHARMACOLOGY ].
Of the total number of subjects in clinical studies of viagra jeaeai, 18% were 65 years and older, while 2% were 75 years and older.
No overall differences in safety or efficacy were observed between older ( > 65 years of age) and younger ( In studies with healthy volunteers of single doses up to 800 mg, adverse reactions were similar to those seen at lower doses but incidence 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.
Consistent with its known effects on the nitric oxide/cGMP pathway [see CLINICAL PHARMACOLOGY ], viagra jeaeai was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using nitric oxide donors such as organic nitrates or organic nitrites in any form either regularly and/or intermittently is therefore contraindicated.
After patients have taken viagra jeaeai, it is unknown when nitrates, if necessary, can be safely administered.
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 co-administered at this time point [see DOSAGE AND ADMINISTRATION , DRUG INTERACTIONS , and CLINICAL PHARMACOLOGY ].
viagra jeaeai is contraindicated in patients with a known hypersensitivity to sildenafil, as contained in viagra jeaeai and REVATIO, or any component of the tablet.
Hypersensitivity reactions have been reported, including rash and urticaria [see ADVERSE REACTIONS ].
Concomitant Guanylate Cyclase (GC) Stimulators.
Do not use viagra jeaeai in patients who are using a GC stimulator, such as riociguat.
PDE5 inhibitors, including viagra jeaeai, may potentiate the hypotensive effects of GC stimulators.
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 enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum.
Sildenafil has no direct relaxant effect on isolated human 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).
Sildenafil is approximately 4,000-fold more selective for PDE5 compared to PDE3.
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 [see Pharmacodynamics ].
In addition to human corpus cavernosum smooth muscle, PDE5 is also found in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle, brain, heart, liver, kidney, lung, pancreas, prostate, bladder, testis, and seminal vesicle.
The inhibition of PDE5 in some of these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of NO observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo.
Effects of viagra jeaeai on Erectile Response.
In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan®), after viagra jeaeai administration compared with placebo.
Most studies assessed the efficacy of viagra jeaeai approximately 60 minutes post dose.
The erectile response, as assessed by RigiScan®, generally increased with increasing sildenafil dose and plasma concentration.
The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours.
Effects of viagra jeaeai on Blood Pressure.
Single oral doses of sildenafil (100 mg) administered to healthy volunteers produced decreases in sitting blood pressure (mean maximum decrease in systolic/diastolic blood pressure of 8.
The decrease in sitting blood pressure was most notable approximately 1-2 hours after dosing, and was not different than placebo at 8 hours.
Similar effects on blood pressure were noted with 25 mg, 50 mg and 100 mg of viagra jeaeai, 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 ].
Figure 1: Mean Change from Baseline in Sitting Systolic Blood Pressure, Healthy Volunteers.
Effects of viagra jeaeai on Blood Pressure When Nitroglycerin is Subsequently 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 years, hepatic impairment (e.
Figure 2: Mean Standing Systolic Blood Pressure Change from Baseline.
Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.
Outliers were defined as subjects with a standing systolic blood pressure of 30 mmHg at one or more timepoints.
There were no subjects treated with viagra jeaeai 25 mg who had a standing SBP 30mmHg following viagra jeaeai 25 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and two subjects with a decrease from baseline in standing systolic BP > 30 mmHg following both viagra jeaeai and placebo.
No severe adverse events potentially related to blood pressure effects were reported in this group.
Of the four subjects who received viagra jeaeai 100 mg in the first part of this study, a severe adverse event related to blood pressure effect was reported in one patient (postural hypotension that began 35 minutes after dosing with viagra jeaeai with symptoms lasting for 8 hours), and mild adverse events potentially related to blood pressure effects were reported in two others (dizziness, headache and fatigue at 1 hour after dosing; and dizziness, lightheadedness and nausea at 4 hours after dosing).
There were no reports of syncope among these patients.
For these four subjects, the placebo-subtracted mean maximum decreases from baseline in supine and standing systolic blood pressures were 14.
Two of these subjects had a standing SBP Placebo-subtracted mean maximum decrease in systolic blood pressure (mm Hg) viagra jeaeai 50 mg (95% CI) Supine 9.
Figure 3: Mean Standing Systolic Blood Pressure Change from Baseline.
Blood pressure was measured after administration of viagra jeaeai at the same times as those specified for the first doxazosin study.
There were two subjects who had a standing SBP of 30mmHg following viagra jeaeai 50 mg and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both viagra jeaeai 50 mg and placebo.
There were no severe adverse events potentially related to blood pressure and no episodes of syncope reported in this study.
Study 3: viagra jeaeai with Doxazosin.
In the third study, a single oral dose of viagra jeaeai 100 mg or matching placebo was administered in a 3-period crossover design to 20 generally healthy males with BPH.
In dose period 1, subjects were administered open-label doxazosin and a single dose of viagra jeaeai 50 mg simultaneously, after at least 14 consecutive days of doxazosin.
If a subject did not successfully complete this first dosing period, he was discontinued from the study.
Subjects who had successfully completed the previous doxazosin interaction study (using viagra jeaeai 50 mg), including no significant hemodynamic adverse events, were allowed to skip dose period 1.
Treatment with doxazosin continued for at least 7 days after dose period 1.
Thereafter, viagra jeaeai 100 mg or matching placebo was administered simultaneously with doxazosin 4 mg (14 subjects) or doxazosin 8 mg (6 subjects) in standard crossover fashion.
The mean subject age in this study was 66.
Twenty-five subjects were screened.
Two were discontinued after study period 1: one failed to meet pre-dose screening qualifications and the other experienced symptomatic hypotension as a moderately severe adverse event 30 minutes after dosing with open-label viagra jeaeai 50 mg.
Of the twenty subjects who were ultimately assigned to treatment, a total of 13 subjects successfully completed dose period 1, and seven had successfully completed the previous doxazosin study (using viagra jeaeai 50 mg).
For the 20 subjects who received viagra jeaeai 100 mg and matching placebo, the placebo-subtracted mean maximum decreases from baseline (95% CI) in systolic blood pressure were as follows: Placebo-subtracted mean maximum decrease in systolic blood pressure (mm Hg) viagra jeaeai 100 mg Supine 7.
Figure 4: Mean Standing Systolic Blood Pressure Change from Baseline.
Blood pressure was measured after administration of viagra jeaeai at the same times as those specified for the previous doxazosin studies.
There were three subjects who had a standing SBP of 30 mmHg following viagra jeaeai 100 mg, one subject with a decrease from baseline in standing systolic BP > 30 mmHg following placebo and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both viagra jeaeai and placebo.
While there were no severe adverse events potentially related to blood pressure reported in this study, one subject reported moderate vasodilatation after both viagra jeaeai 50 mg and 100 mg.
There were no episodes of syncope reported in this study.
Effect of viagra jeaeai on Blood Pressure When Co-administered with Anti-hypertensives.
When viagra jeaeai 100 mg oral was co-administered with amlodipine, 5 mg or 10 mg oral, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic.
Effect of viagra jeaeai on Blood Pressure When Co-administered with Alcohol.
viagra jeaeai (50 mg) did not potentiate the hypotensive effect of alcohol (0.
The maximum observed decrease in systolic blood pressure was -18.
The maximum observed decrease in diastolic blood pressure was -17.
There were no reports of postural dizziness or orthostatic hypotension.
The maximum recommended dose of 100 mg sildenafil was not evaluated in this study [see DRUG INTERACTIONS ].
Effects of viagra jeaeai on Cardiac Parameters.
Single oral doses of sildenafil up to 100 mg produced no clinically relevant changes in the ECGs of normal male volunteers.
Studies have produced relevant data on the effects of viagra jeaeai on cardiac output.
In one small, open-label, uncontrolled, pilot study, eight patients with stable ischemic heart disease underwent Swan-Ganz catheterization.
A total dose of 40 mg sildenafil was administered by four intravenous infusions.
The results from this pilot study are shown in Table 3; the mean resting systolic and diastolic blood pressures decreased by 7% and 10% compared to baseline in these patients.
Mean resting values for right atrial pressure, pulmonary artery pressure, pulmonary artery occluded pressure and cardiac output decreased by 28%, 28%, 20% and 7% respectively.
Even though this total dosage produced plasma sildenafil concentrations which were approximately 2 to 5 times higher than the mean maximum plasma concentrations following a single oral dose of 100 mg in healthy male volunteers, the hemodynamic response to exercise was preserved in these patients.
Table 3: Hemodynamic Data in Patients with Stable Ischemic Heart Disease after Intravenous Administration of 40 mg of Sildenafil Means ± SD At rest After 4 minutes of exercise N Baseline (B2) n Sildenafil (D1) n Baseline n Sildenafil PAOP (mmHg) 8 8.
In a double-blind study, 144 patients with erectile dysfunction and chronic stable angina limited by exercise, not receiving chronic oral nitrates, were randomized to a single dose of placebo or viagra jeaeai 100 mg 1 hour prior to exercise testing.
The primary endpoint was time to limiting angina in the evaluable cohort.
The mean times (adjusted for baseline) to onset of limiting angina were 423.
These results demonstrated that the effect of viagra jeaeai on the primary endpoint was statistically non-inferior to placebo.
Effects of viagra jeaeai on Vision.
At single oral doses of 100 mg and 200 mg, transient dose-related impairment of color discrimination 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.
Subjects in the study reported this finding as difficulties in discriminating blue/green.
An evaluation of visual function at doses up to twice the maximum recommended dose revealed no effects of viagra jeaeai on visual acuity, intraocular pressure, or pupillometry.
Effects of viagra jeaeai on Sperm.
There was no effect on sperm motility or morphology after single 100 mg oral doses of viagra jeaeai in healthy volunteers.
viagra jeaeai is rapidly absorbed after oral administration, with a mean absolute bioavailability of 41% (range 2563%).
The pharmacokinetics of sildenafil are dose-proportional over the recommended dose range.
It is eliminated predominantly by hepatic metabolism (mainly CYP3A4) and is converted to an active metabolite with properties similar to the parent, sildenafil.
Both sildenafil and the metabolite have terminal half lives of about 4 hours.
Mean sildenafil plasma concentrations measured after the administration of a single oral dose of 100 mg to healthy male volunteers is depicted below: Figure 5: Mean Sildenafil Plasma Concentrations in Healthy Male Volunteers.
viagra jeaeai 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 jeaeai 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.
Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins.
Protein binding is independent of total drug concentrations.
Based upon measurements of sildenafil in semen of healthy volunteers 90 minutes after dosing, less than 0.
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.
Pharmacokinetics in Special Populations.
Geriatrics : Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy younger volunteers (18-45 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 [see DOSAGE AND ADMINISTRATION , and Use In Specific Populations ] Renal Impairment : 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 jeaeai (50 mg) were not altered.
In volunteers with severe (CLcr 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 [see DOSAGE AND ADMINISTRATION ].
Effects of Other Drugs on viagra jeaeai.
Sildenafil metabolism is principally mediated by CYP3A4 (major route) and CYP2C9 (minor route).
Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.
The concomitant use of erythromycin or strong CYP3A4 inhibitors (e.
Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with viagra jeaeai (50 mg) to healthy volunteers.
When a single 100 mg dose of viagra jeaeai was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 160% increase in sildenafil Cmax and a 182% increase in sildenafil AUC.
In addition, in a study performed in healthy male volunteers, co-administration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200 mg tid) with viagra jeaeai (100 mg single dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC.
viagra jeaeai had no effect on saquinavir pharmacokinetics.
A stronger CYP3A4 inhibitor such as ketoconazole or itraconazole could be expected to have greater effect than that seen with saquinavir.
Population pharmacokinetic data from patients in clinical trials also indicated a reduction in sildenafil clearance when it was co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS ].
In another study in healthy male volunteers, co-administration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with viagra jeaeai (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1000% (11-fold) increase in sildenafil plasma AUC.
At 24 hours the plasma levels of sildenafil were still approximately 200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone.
This is consistent with ritonavir's marked effects on a broad range of P450 substrates.
viagra jeaeai had no effect on ritonavir pharmacokinetics [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS ].
Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels.
In a study of healthy male volunteers, co-administration of sildenafil at steady state (80 mg t.
Concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma levels of sildenafil.
Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of viagra jeaeai.
In healthy male volunteers, there was no evidence of a clinically significant effect of azithromycin (500 mg daily for 3 days) on the systemic exposure of sildenafil or its major circulating metabolite.
Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers.
The AUC of the active metabolite, N-desmethyl sildenafil, was increased 62% by loop and potassium-sparing diuretics and 102% by nonspecific beta-blockers.
These effects on the metabolite are not expected to be of clinical consequence.
Effects of viagra jeaeai on Other Drugs.
Sildenafil is a weak inhibitor of the CYP isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 ?M).
Given sildenafil peak plasma concentrations of approximately 1 ?M after recommended doses, it is unlikely that viagra jeaeai will alter the clearance of substrates of these isoenzymes.
No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9.
In a study of healthy male volunteers, sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.
viagra jeaeai (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).
Sildenafil at steady state, at a dose not approved for the treatment of erectile dysfunction (80 mg t.
In clinical studies, viagra jeaeai was assessed for its effect on the ability of men with erectile dysfunction (ED) to engage in sexual activity and in many cases specifically on the ability to achieve and maintain an erection sufficient for satisfactory sexual activity.
viagra jeaeai was evaluated primarily at doses of 25 mg, 50 mg and 100 mg in 21 randomized, double-blind, placebo-controlled trials of up to 6 months in duration, using a variety of study designs (fixed dose, titration, parallel, crossover).
viagra jeaeai was administered to more than 3,000 patients aged 19 to 87 years, with ED of various etiologies (organic, psychogenic, mixed) with a mean duration of 5 years.
viagra jeaeai demonstrated statistically significant improvement compared to placebo in all 21 studies.
The studies that established benefit demonstrated improvements in success rates for sexual intercourse compared with placebo.
Efficacy Endpoints in Controlled Clinical Studies.
The effectiveness of viagra jeaeai was evaluated in most studies using several assessment instruments.
The primary measure in the principal studies was a sexual function questionnaire (the International Index of Erectile Function -IIEF) administered during a 4-week treatment-free run-in period, at baseline, at follow-up visits, and at the end of double-blind, placebo-controlled, at-home treatment.
Two of the questions from the IIEF served as primary study endpoints; categorical responses were elicited to questions about (1) the ability to achieve erections sufficient for sexual intercourse and (2) the maintenance of erections after penetration.
The patient addressed both questions at the final visit for the last 4 weeks of the study.
The possible categorical responses to these questions were (0) no attempted intercourse, (1) never or almost never, (2) a few times, (3) sometimes, (4) most times, and (5) almost always or always.
Also collected as part of the IIEF was information about other aspects of sexual function, including information on erectile function, orgasm, desire, satisfaction with intercourse, and overall sexual satisfaction.
Sexual function data were also recorded by patients in a daily diary.
In addition, patients were asked a global efficacy question and an optional partner questionnaire was administered.
Efficacy Results from Controlled Clinical Studies.
The effect on one of the major end points, maintenance of erections after penetration, is shown in Figure 6, for the pooled results of 5 fixed-dose, dose-response studies of greater than one month duration, showing response according to baseline function.
Results with all doses have been pooled, but scores showed greater improvement at the 50 and 100 mg doses than at 25 mg.
The pattern of responses was similar for the other principal question, the ability to achieve an erection sufficient for intercourse.
The titration studies, in which most patients received 100 mg, showed similar results.
Figure 6 shows that regardless of the baseline levels of function, subsequent function in patients treated with viagra jeaeai was better than that seen in patients treated with placebo.
At the same time, on-treatment function was better in treated patients who were less impaired at baseline.
Figure 6: Effect of viagra jeaeai and Placebo on Maintenance of Erection by Baseline Score.
The frequency of patients reporting improvement of erections in response to a global question in four of the randomized, double-blind, parallel, placebo-controlled fixed dose studies (1797 patients) of 12 to 24 weeks duration is shown in Figure 7.
These patients had erectile dysfunction at baseline that was characterized by median categorical scores of 2 (a few times) on principal IIEF questions.
Erectile dysfunction was attributed to organic (58%; generally not characterized, but including diabetes and excluding spinal cord injury), psychogenic (17%), or mixed (24%) etiologies.
Sixty-three percent, 74%, and 82% of the patients on 25 mg, 50 mg and 100 mg of viagra jeaeai, respectively, reported an improvement in their erections, compared to 24% on placebo.
In the titration studies (n=644) (with most patients eventually receiving 100 mg), results were similar.
Figure 7: Percentage of Patients Reporting an Improvement in Erections.
The patients in studies had varying degrees of ED.
One-third to one-half of the subjects in these studies reported successful intercourse at least once during a 4-week, treatment-free run-in period.
In many of the studies, of both fixed dose and titration designs, daily diaries were kept by patients.
In these studies, involving about 1600 patients, analyses of patient diaries showed no effect of viagra jeaeai on rates of attempted intercourse (about 2 per week), but there was clear treatment-related improvement in sexual function: per patient weekly success rates averaged 1.
During 3 to 6 months of double-blind treatment or longer-term (1 year), open-label studies, few patients withdrew from active treatment for any reason, including lack of effectiveness.
At the end of the long-term study, 88% of patients reported that viagra jeaeai improved their erections.
Men with untreated ED had relatively low baseline scores for all aspects of sexual function measured (again using a 5-point scale) in the IIEF.
viagra jeaeai improved these aspects of sexual function: frequency, firmness and maintenance of erections; frequency of orgasm; frequency and level of desire; frequency, satisfaction and enjoyment of intercourse; and overall relationship satisfaction.
One randomized, double-blind, flexible-dose, placebo-controlled study included only patients with erectile dysfunction attributed to complications of diabetes mellitus (n=268).
As in the other titration studies, patients were started on 50 mg and allowed to adjust the dose up to 100 mg or down to 25 mg of viagra jeaeai; all patients, however, were receiving 50 mg or 100 mg at the end of the study.
There were highly statistically significant improvements on the two principal IIEF questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) on viagra jeaeai compared to placebo.
On a global improvement question, 57% of viagra jeaeai patients reported improved erections versus 10% on placebo.
Diary data indicated that on viagra jeaeai, 48% of intercourse attempts were successful versus 12% on placebo.
One randomized, double-blind, placebo-controlled, crossover, flexible-dose (up to 100 mg) study of patients with erectile dysfunction resulting from spinal cord injury (n=178) was conducted.
The changes from baseline in scoring on the two end point questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) were highly statistically significantly in favor of viagra jeaeai.
On a global improvement question, 83% of patients reported improved erections on viagra jeaeai versus 12% on placebo.
Diary data indicated that on viagra jeaeai, 59% of attempts at sexual intercourse were successful compared to 13% on placebo.
Across all trials, viagra jeaeai improved the erections of 43% of radical prostatectomy patients compared to 15% on placebo.
Subgroup analyses of responses to a global improvement question in patients with psychogenic etiology in two fixed-dose studies (total n=179) and two titration studies (total n=149) showed 84% of viagra jeaeai patients reported improvement in erections compared with 26% of placebo.
The changes from baseline in scoring on the two end point questions (frequency of successful penetration during sexual activity and maintenance of erections after penetration) were highly statistically significantly in favor of viagra jeaeai.
Diary data in two of the studies (n=178) showed rates of successful intercourse per attempt of 70% for viagra jeaeai and 29% for placebo.
Efficacy Results in Subpopulations in Controlled Clinical Studies.
A review of population subgroups demonstrated efficacy regardless of baseline severity, etiology, race and age.
viagra jeaeai was effective in a broad range of ED patients, including those with a history of coronary artery disease, hypertension, other cardiac disease, peripheral vascular disease, diabetes mellitus, depression, coronary artery bypass graft (CABG), radical prostatectomy, transurethral resection of the prostate (TURP) and spinal cord injury, and in patients taking antidepressants/antipsychotics and anti-hypertensives/diuretics.
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