What Is Sildenafil Citrate?

Patients treated with sildenafil were followed for a median of 4.6 years (range 2 days to 8.6 years). Mortality during the long-term study, by originally assigned dose, is shown in Figure 6: During the study, there were 42 reported deaths with 37 of these deaths reported prior to a decision to titrate subjects to a lower dosage because of a finding of increased mortality with increasing sildenafil citrate doses.

For the survival analysis which included 37 deaths, the hazard ratio for high dose compared to low dose was 3.9, p=0.007. Causes of death were typical of patients with PAH.

What Are Warnings and Precautions for Sildenafil?

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In postmarketing experience with sildenafil at doses indicated for erectile dysfunction, serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, pulmonary hemorrhage, and subarachnoid and intracerebral hemorrhages have been reported in temporal association with the use of the drug. 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 sildenafil without sexual activity. Others were reported to have occurred hours to days after use concurrent with sexual activity.

How can I get Viagra to work?

It is not possible to determine whether these events are related directly to sildenafil, to sexual activity, to the patient’s underlying cardiovascular disease, or to a combination of these or other factors. Concomitant use of sildenafil citrate with nitrates in any form is contraindicated. Concomitant use of sildenafil citrate with ritonavir and other potent CYP3A inhibitors is not recommended. In drug-drug interaction studies, sildenafil (25 mg, 50 mg, or 100 mg) and the alpha-blocker doxazosin (4 mg or 8 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy. In these study populations, mean additional reductions of supine systolic and diastolic blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, respectively, were observed. Clinical studies of sildenafil citrate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. There is no FDA guidance on the use of Sildenafil with respect to specific gender populations. There is no FDA guidance on the use of Sildenafil with respect to specific racial populations.

No dose adjustment is required (including severe impairment CLcr < 30 mL/min).

IV Compatibility

The overall frequency of discontinuation in sildenafil citrate-treated patients 20 mg TID was 3% and was the same for the placebo group. In Study 1, the adverse reactions that were reported by at least 3% of sildenafil citrate-treated patients (20 mg TID) and were more frequent in sildenafil citrate-treated patients than in placebo-treated patients are shown in Table 1. Adverse reactions were generally transient and mild to moderate in nature. At doses higher than the recommended 20 mg TID, there was a greater incidence of some adverse reactions including flushing, diarrhea, myalgia and visual disturbances. Visual disturbances were identified as mild and transient, and were predominately color-tinge to vision, but also increased sensitivity to light or blurred vision.

Is Viagra safe to use?

The incidence of retinal hemorrhage with sildenafil citrate 20 mg TID was 1.4% versus 0% placebo and for all sildenafil citrate doses studied was 1.9% versus 0% placebo. The incidence of eye hemorrhage at both 20 mg TID and at all doses studied was 1.4% for sildenafil citrate versus 1.4% for placebo. The patients experiencing these reactions had risk factors for hemorrhage including concurrent anticoagulant therapy. In a placebo-controlled fixed dose titration study (Study 2) of sildenafil citrate (starting with recommended dose of 20 mg TID and increased to 40 mg TID and then 80 mg TID) as an adjunct to intravenous epoprostenol in patients with PAH, the adverse reactions that were more frequent in the sildenafil citrate + epoprostenol group than in the epoprostenol group (greater than 6% difference) are shown in Table 2 . The following adverse reactions have been identified during post approval use of * Sildenafil (marketed for both PAH and erectile dysfunction). No dose adjustment for mild to moderate impairment is required. There is no FDA guidance on the use of Sildenafil in women of reproductive potentials and males. There is no FDA guidance one the use of Sildenafil in patients who are immunocompromised.

FDA Package Insert for Sildenafil contains no information regarding drug monitoring.

• Sildenafil can enhance the effects of other blood pressure medications.
• The drug’s safety profile is well-studied with many clinical trials.
• Cardiovascular health is an important consideration when taking sildenafil.
• Long-term use requires monitoring for adverse reactions.
• Patient education helps reduce risks and optimize dosage.
• Generic sildenafil offers a cost-effective alternative to branded Viagra.
• Regular health assessments can ensure safe usage.

There is limited information about the IV Compatibility. In studies with healthy volunteers of single doses up to 800 mg, adverse events were similar to those seen at lower doses but rates and severities were increased. In cases of overdose, standard supportive measures should be adopted as required.

How Supplied

Mean additional reductions of standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were also observed. There were infrequent reports of patients who experienced symptomatic postural hypotension. These reports included dizziness and light-headedness, but not syncope. When sildenafil 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. There are no adequate and well-controlled studies of sildenafil in pregnant women.

How is sildenafil supplied (dosage forms)?

No evidence of teratogenicity, embryotoxicity, or fetotoxicity was observed in pregnant rats or rabbits dosed with sildenafil 200 mg/kg/day during organogenesis, a level that is, on a mg/m2 basis, 32- and 68-times, respectively, the recommended human dose (RHD) of 20 mg three times a day. In a rat pre- and postnatal development study, the no-observed-adverse-effect dose was 30 mg/kg/day (equivalent to 5-times the RHD on a mg/m2 basis). Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sildenafil in women who are pregnant. The safety and efficacy of sildenafil citrate during labor and delivery has not been studied. It is not known if sildenafil or its metabolites are excreted in human breast milk. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is not eliminated in the urine. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation.

In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation. Studies in vitro have shown that sildenafil is selective for PDE-5. Its effect is more potent on PDE-5 than on other known phosphodiesterases (10-fold for PDE6, greater than 80-fold for PDE1, greater than 700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE-5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility.

• Sildenafil citrate was first approved by the FDA in 1998.
• Its brand name is Viagra, but generic versions are available.
• The drug is available in tablets of various strengths, typically 25-100 mg.
• It can be prescribed for both men and in specific cases, women.
• Proper dosage varies based on health status and response.
• Use caution in patients with heart problems or low blood pressure.
• It is not a hormone or a testosterone booster.

Sildenafil is only about 10-fold as potent for PDE-5 compared to PDE6, an enzyme found in the retina and involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels. In addition to pulmonary vascular smooth muscle and the corpus cavernosum, PDE-5 is also found in other tissues including vascular and visceral smooth muscle and in platelets. The inhibition of PDE-5 in these tissues by sildenafil may be the basis for the enhanced platelet anti-aggregatory activity of nitric oxide observed in vitro, and the mild peripheral arterial-venous dilatation in vivo.

What Other Drugs Interact with Sildenafil?

Because many drugs are excreted in human milk, caution should be exercised when sildenafil citrate is administered to a nursing woman. In a randomized, double-blind, multi-center, placebo-controlled, parallel-group, dose-ranging study, 234 patients with PAH, aged 1 to 17 years, body weight greater than or equal to 8 kg, were randomized, on the basis of body weight, to three dose levels of sildenafil citrate, or placebo, for 16 weeks of treatment. Most patients had mild to moderate symptoms at baseline: WHO Functional Class I (32%), II (51%), III (15%), or IV (0.4%). One-third of patients had primary PAH; two-thirds had secondary PAH (systemic-to-pulmonary shunt in 37%; surgical repair in 30%). Sixty-two percent of patients were female.

Treatment & Diagnosis

The primary objective of the study was to assess the effect of sildenafil citrate on exercise capacity as measured by cardiopulmonary exercise testing in pediatric patients developmentally able to perform the test (n = 115). Administration of sildenafil citrate did not result in a statistically significant improvement in exercise capacity in those patients. No patients died during sildenafil citrate 120 mg the 16-week controlled study. After completing the 16-week controlled study, a patient originally randomized to sildenafil citrate remained on his/her dose of sildenafil citrate or, if originally randomized to placebo, was randomized to low-, medium-, or high-dose sildenafil citrate. After all patients completed 16 weeks of follow-up in the controlled study, the blind was broken and doses were adjusted as clinically indicated. Sildenafil is also marketed as Sildenafil citrate® for erectile dysfunction.