Recommended Topic Related To:

Viagra

"For men with low testosterone, taking testosterone along with Viagra may not help their erections more than if they only took Viagra, a new study shows.

“There were lots of reasons to think that it would work," Boston University rese"...

Viagra

Side Effects
Interactions

SIDE EFFECTS

Clinical Trials

VIAGRA (sildenafil citrate) 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 events for VIAGRA (sildenafil citrate) (2.5%) was not significantly different from placebo (2.3%). The adverse events were generally transient and mild to moderate in nature.

In trials of all designs, adverse events reported by patients receiving VIAGRA (sildenafil citrate) were generally similar. In fixed-dose studies, the incidence of some adverse events increased with dose. The nature of the adverse events in flexible-dose studies, which more closely reflect the recommended dosage regimen, was similar to that for fixed-dose studies.

When VIAGRA (sildenafil citrate) was taken as recommended (on an as-needed basis) in flexible-dose, placebo-controlled clinical trials, the following adverse events were reported:

TABLE 2. ADVERSE EVENTS REPORTED BY ≥ 2% OF PATIENTS TREATED WITH VIAGRA (sildenafil citrate) AND MORE FREQUENT ON DRUG THAN PLACEBO IN PRN FLEXIBLE-DOSE PHASE II/III STUDIES

Adverse Event Percentage of Patients VIAGRA
N=734
Reporting Event PLACEBO
N=725
Headache 16% 4%
Flushing 10% 1%
Dyspepsia 7% 2%
Nasal Congestion 4% 2%
Urinary Tract Infection 3% 2%
Abnormal Vision 3% 0%
Diarrhea 3% 1%
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.

Other adverse reactions occurred at a rate of > 2%, but equally common on placebo: respiratory tract infection, back pain, flu syndrome, and arthralgia.

In fixed-dose studies, dyspepsia (17%) and abnormal vision (11%) were more common at 100 mg than at lower doses. At doses above the recommended dose range, adverse events were similar to those detailed above but generally were reported more frequently.

The following events occurred in < 2% of patients in controlled clinical trials; a causal relationship to VIAGRA (sildenafil citrate) is uncertain. Reported events include those with a plausible relation to drug use; omitted are minor events and reports too imprecise to be meaningful:

Body as a whole: face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain, accidental injury.

Cardiovascular: angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension, myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal electrocardiogram, cardiomyopathy.

Digestive: vomiting, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, liver function tests abnormal, rectal hemorrhage, gingivitis.

Hemic and Lymphatic: anemia and leukopenia.

Metabolic and Nutritional: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemic reaction, hypernatremia.

Musculoskeletal: arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis.

Nervous: ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal dreams, reflexes decreased, hypesthesia.

Respiratory: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased.

Skin and Appendages: urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.

Special Senses: sudden decrease or loss of hearing, mydriasis, conjunctivitis, photophobia, tinnitus, eye pain, ear pain, eye hemorrhage, cataract, dry eyes.

Urogenital: cystitis, nocturia, urinary frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema and anorgasmia.

Post-Marketing Experience

Cardiovascular and cerebrovascular

Serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of VIAGRA (sildenafil citrate) . Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of VIAGRA (sildenafil citrate) without sexual activity. Others were reported to have occurred hours to days after the use of VIAGRA (sildenafil citrate) and sexual activity. It is not possible to determine whether these events are related directly to VIAGRA (sildenafil citrate) , to sexual activity, to the patient's underlying cardiovascular disease, to a combination of these factors, or to other factors (see WARNINGS for further important cardiovascular information).

Special senses

Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including VIAGRA (sildenafil citrate) . In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of VIAGRA (sildenafil citrate) , to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors (see PATIENT INFORMATION).

Other events

Other events reported post-marketing to have been observed in temporal association with VIAGRA (sildenafil citrate) and not listed in the clinical trial adverse reactions section above include:

Nervous: seizure, seizure recurrence, anxiety, and transient global amnesia.

Urogenital: prolonged erection, priapism (see WARNINGS), and hematuria.

Special Senses: diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal vascular disease or bleeding, vitreous detachment/traction, paramacular edema and epistaxis.

Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of phosphodiesterase type 5 (PDE5) inhibitors, including VIAGRA (sildenafil citrate) . Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors, to the patient's underlying vascular risk factors or anatomical defects, to a combination of these factors, or to other factors (see PATIENT INFORMATION).

Read the Viagra (sildenafil citrate) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Effects of Other Drugs on VIAGRA (sildenafil citrate)

In vitro studies: Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.

In vivo studies: Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when coadministered with VIAGRA (sildenafil citrate) (50 mg) to healthy volunteers.

When a single 100 mg dose of VIAGRA (sildenafil citrate) was administered with erythromycin, a specific CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 182% increase in sildenafil systemic exposure (AUC). In addition, in a study performed in healthy male volunteers, coadministration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200 mg tid) with VIAGRA (sildenafil citrate) (100 mg single dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC. VIAGRA (sildenafil citrate) had no effect on saquinavir pharmacokinetics. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole would be expected to have still greater effects, and population data from patients in clinical trials did indicate a reduction in sildenafil clearance when it was coadministered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) (see DOSAGE AND ADMINISTRATION).

In another study in healthy male volunteers, coadministration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with VIAGRA (sildenafil citrate) (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 (sildenafil citrate) had no effect on ritonavir pharmacokinetics (see DOSAGE AND ADMINISTRATION).

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.i.d.) with endothelin receptor antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9 and possibly of cytochrome P450 2C19) at steady state (125 mg b.i.d.) resulted in a 63% decrease of sildenafil AUC and a 55% decrease in sildenafil Cmax. 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 (sildenafil citrate) .

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 (sildenafil citrate) on Other Drugs

In vitro studies: Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 µM). Given sildenafil peak plasma concentrations of approximately 1 µM after recommended doses, it is unlikely that VIAGRA (sildenafil citrate) will alter the clearance of substrates of these isoenzymes.

In vivo studies: Three double-blind, placebo-controlled, randomized, two-way crossover studies were conducted to assess the interaction of VIAGRA (sildenafil citrate) with doxazosin, an alpha-adrenergic blocking agent.

In the first study, a single oral dose of VIAGRA (sildenafil citrate) 100 mg or matching placebo was administered in a 2-period crossover design to 4 generally healthy males with benign prostatic hyperplasia (BPH). Following at least 14 consecutive daily doses of doxazosin, VIAGRA (sildenafil citrate) 100 mg or matching placebo was administered simultaneously with doxazosin. Following a review of the data from these first 4 subjects (details provided below), the VIAGRA (sildenafil citrate) dose was reduced to 25 mg. Thereafter, 17 subjects were treated with VIAGRA (sildenafil citrate) 25 mg or matching placebo in combination with doxazosin 4 mg (15 subjects) or doxazosin 8mg (2 subjects). The mean subject age was 66.5 years.

For the 17 subjects who received VIAGRA (sildenafil citrate) 25 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 25 mg
Supine 7.4 (-0.9, 15.7)
Standing 6.0 (-0.8, 12.8)

Figure 5: Mean Standing Systolic Blood Pressure Change from Baseline

Mean Standing Systolic Blood Pressure Change from Baseline - Illustration

Blood pressure was measured immediately pre-dose and at 15, 30, 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours after VIAGRA (sildenafil citrate) or matching placebo. Outliers were defined as subjects with a standing systolic blood pressure of < 85 mmHg or a decrease from baseline in standing systolic blood pressure of > 30 mmHg at one or more timepoints. There were no subjects treated with VIAGRA (sildenafil citrate) 25 mg who had a standing SBP < 85mmHg. There were three subjects with a decrease from baseline in standing systolic BP > 30mmHg following VIAGRA (sildenafil citrate) 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 (sildenafil citrate) and placebo. No severe adverse events potentially related to blood pressure effects were reported in this group.

Of the four subjects who received VIAGRA (sildenafil citrate) 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 (sildenafil citrate) 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 14.8 mmHg and 21.5 mmHg, respectively. Two of these subjects had a standing SBP < 85mmHg. Both of these subjects were protocol violators, one due to a low baseline standing SBP, and the other due to baseline orthostatic hypotension.

In the second study, a single oral dose of VIAGRA (sildenafil citrate) 50 mg or matching placebo was administered in a 2-period crossover design to 20 generally healthy males with BPH. Following at least 14 consecutive days of doxazosin, VIAGRA (sildenafil citrate) 50mg or matching placebo was administered simultaneously with doxazosin 4 mg (17 subjects) or with doxazosin 8 mg (3 subjects). The mean subject age in this study was 63.9 years.

Twenty subjects received VIAGRA (sildenafil citrate) 50 mg, but only 19 subjects received matching placebo. One patient discontinued the study prematurely due to an adverse event of hypotension following dosing with VIAGRA (sildenafil citrate) 50 mg. This patient had been taking minoxidil, a potent vasodilator, during the study.

For the 19 subjects who received both VIAGRA (sildenafil citrate) 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 50 mg (95% CI)
Supine 9.08 (5.48, 12.68)
Standing 11.62 (7.34, 15.90)

Figure 6: Mean Standing Systolic Blood Pressure Change from Baseline

Mean Standing Systolic Blood Pressure Change from Baseline - Illustration

Blood pressure was measured after administration of VIAGRA (sildenafil citrate) at the same times as those specified for the first doxazosin study. There were two subjects who had a standing SBP of < 85 mmHg. In these two subjects, hypotension was reported as a moderately severe adverse event, beginning at approximately 1 hour after administration of VIAGRA (sildenafil citrate) 50 mg and resolving after approximately 7.5 hours. There was one subject with a decrease from baseline in standing systolic BP > 30mmHg following VIAGRA (sildenafil citrate) 50 mg and one subject with a decrease from baseline in standing systolic BP > 30 mmHg following both VIAGRA (sildenafil citrate) 50 mg and placebo. There were no severe adverse events potentially related to blood pressure and no episodes of syncope reported in this study.

In the third study, a single oral dose of VIAGRA (sildenafil citrate) 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 (sildenafil citrate) 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 (sildenafil citrate) 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 (sildenafil citrate) 100mg 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 66.4 years.

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 (sildenafil citrate) 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 (sildenafil citrate) 50 mg).

For the 20 subjects who received VIAGRA (sildenafil citrate) 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 100 mg
Supine 7.9 (4.6, 11.1)
Standing 4.3 (-1.8,10.3)

Figure 7: Mean Standing Systolic Blood Pressure Change from Baseline

Mean Standing Systolic Blood Pressure Change from Baseline - Illustration

Blood pressure was measured after administration of VIAGRA (sildenafil citrate) at the same times as those specified for the previous doxazosin studies. There were three subjects who had a standing SBP of < 85 mmHg. All three were taking VIAGRA (sildenafil citrate) 100 mg, and all three reported mild adverse events at the time of reductions in standing SBP, including vasodilation and lightheadedness. There were four subjects with a decrease from baseline in standing systolic BP > 30mmHg following VIAGRA (sildenafil citrate) 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 (sildenafil citrate) 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 (sildenafil citrate) 50 mg and 100 mg. There were no episodes of syncope reported in this study.

When VIAGRA (sildenafil citrate) 100 mg oral was coadministered 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.

No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolized by CYP2C9.

VIAGRA (sildenafil citrate) (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).

VIAGRA (sildenafil citrate) (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08%.

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.

Sildenafil at steady state (80 mg t.i.d.) resulted in a 50% increase in AUC and a 42% increase in Cmax of bosentan (125 mg b.i.d.).

Read the Viagra Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 3/21/2014
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
A A A

Viagra - User Reviews

Viagra User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Viagra sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.



Sex & Relationships

Get tips to boost your love life.