Off-Label Uses of Sildenafil 60mg

There is insufficient information about the effects of sildenafil on the breastfed infant and no information on the effects of sildenafil on milk production.

The Takeaway

This effect was not seen in idiopathic PAH (REVATIO 3%, placebo 2%) patients. The incidence of epistaxis was also higher in REVATIO-treated patients with a concomitant oral vitamin K antagonist (9% versus 2% in those not treated with concomitant vitamin K antagonist). The safety of REVATIO is unknown in patients with bleeding disorders or active peptic ulceration. When used to treat erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported post marketing in temporal association with the use of PDE-5 inhibitors, including sildenafil. Most patients had underlying anatomic or vascular risk factors for developing NAION, including low cup to disc ratio (“crowded disc”).

Long-term use

Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking REVATIO. There are no controlled clinical data on the safety or efficacy of REVATIO in patients with retinitis pigmentosa, a minority of whom have genetic disorders of retinal phosphodiesterases. Therefore, use of REVATIO in patients with retinitis pigmentosa is not recommended. Cases of sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, have been reported in temporal association with the use of PDE-5 inhibitors, including REVATIO. In some of the cases, medical conditions and other factors were reported that may have played a role. Limited clinical data during lactation preclude a clear determination of the risk of REVATIO to an infant during lactation.

The safety and efficacy of REVATIO have been established in pediatric patients 1 to 17 years old, for the treatment of PAH (WHO Group I) to improve exercise ability and, in patients too young to perform standard exercising testing, pulmonary hemodynamics thought to underlie improvements in exercise. Use of REVATIO for this indication is supported by evidence from adequate and well-controlled studies in adults with additional PK and safety data in pediatric patients aged 1 year and older [see ADVERSE REACTIONS, Clinical Studies]. The safety and effectiveness of REVATIO have not been established in pediatric patients younger than 1 year of age.

Comparing Drug Interactions

Advise patients taking REVATIO not to take sildenafil pricing VIAGRA or other PDE-5 inhibitors. Advise patients to seek immediate medical attention for a sudden loss of vision in one or both eyes while taking REVATIO. Such an event may be a sign of NAION. Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking REVATIO. These events may be accompanied by tinnitus and dizziness.

Patient resources

Sildenafil was not carcinogenic when administered to rats for up to 24 months at 60 mg/kg/day, a dose resulting in total systemic exposure (AUC) to unbound sildenafil and its major metabolite 33- and 37-times, for male and female rats, respectively, the human exposure at the RHD of 20 mg three times a day. Sildenafil was not carcinogenic when administered to male and female mice for up to 21 and 18 months, respectively, at doses up to a maximally tolerated level of 10 mg/kg/day, a dose equivalent to the RHD on a mg/m² basis. Sildenafil was negative in in vitro bacterial and Chinese hamster ovary cell assays to detect mutagenicity, and in vitro human lymphocytes and in vivo mouse micronucleus assays to detect clastogenicity. There was no impairment of fertility in male or female rats given up to 60 mg sildenafil/kg/day, a dose producing a total systemic exposure (AUC) to unbound sildenafil and its major metabolite of 19- and 38-times for males and females, respectively, the human exposure at the RHD of 20 mg three times a day. Limited published data from randomized controlled trials, case-controlled trials, and case series do not report a clear association with sildenafil and major birth defects, miscarriage, or adverse maternal or fetal outcomes when sildenafil is used during pregnancy. During the conduct of the pediatric studies (STARTS-1 and STARTS-2) [see Clinical Studies], an imbalance in the number of deaths was noted: 5/55 (9.1%), 10/74 (13.5%), and 22/100 (22%) in the sildenafil low, medium, and high dose groups, respectively.

• Common side effects include flushing and nasal congestion.
• Seek emergency help if experiencing prolonged erection.
• Do not use if you are taking nitrates.
• Alcohol consumption can decrease effectiveness.

The causes of death were related to the progression of PAH. This safety observation in pediatrics was not confirmed in a study conducted in adults designed to evaluate this risk (Study A1481324).

• Sildenafil 60mg is one of several doses available.
• Your doctor may adjust the dose based on response.
• Use only the dose prescribed to you.
• Do not self-adjust the medication without medical advice.

Given the beneficial effects on clinical worsening and death observed in adults with increasing doses (Study A1481324) and the expected similarity of disease in pediatrics and adults, a causal association for the observed dose-related effect on mortality in pediatric patients is unlikely, and therefore, the available data support dosing in pediatric patients > 45 kg up to a maximum of 40 mg three times a day. Clinical sildenafil products over the counter studies of REVATIO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. 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 [see CLINICAL PHARMACOLOGY]. No dose adjustment for mild to moderate impairment is required.

• Consult your healthcare provider before starting sildenafil.
• Monitor blood pressure regularly if prescribed anticoagulants.
• Be cautious with activities requiring alertness post-dose.
• Treatment should be part of a broader health plan.

Severe impairment has not been studied [see CLINICAL PHARMACOLOGY]. No dose adjustment is required (including severe impairment CLcr < 30 mL/min) [see CLINICAL PHARMACOLOGY]. 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.

Which Makes You Harder?

It is not possible to determine whether these reported events are related directly to the use of REVATIO, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors. Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking PDE-5 inhibitors, including REVATIO. The safety and efficacy of combinations of REVATIO with VIAGRA or other PDE-5 inhibitors have not been studied. Inform patients taking REVATIO not to take VIAGRA or other PDE-5 inhibitors. If priapism (painful erection greater than 6 hours in duration) is not treated immediately, penile tissue damage and permanent loss of potency could result.

Professional resources

In a small, prematurely terminated study of patients with pulmonary hypertension (PH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported by patients who received REVATIO than by those randomized to placebo. The effectiveness and safety of REVATIO in the treatment of PH secondary to sickle cell disease has not been established. Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use). Inform patients of contraindication of REVATIO with regular and/or intermittent use of organic nitrates. Inform patients that sildenafil is also marketed as VIAGRA for erectile dysfunction. Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see WARNINGS AND PRECAUTIONS]. Phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat. Known hypersensitivity to sildenafil or any component of the tablet, injection, or oral suspension. Hypersensitivity, including anaphylactic reaction, anaphylactic shock and anaphylactoid reaction, has been reported in association with the use of sildenafil.

Sildenafil is an inhibitor of cGMP specific PDE-5 in the smooth muscle of the pulmonary vasculature, where PDE-5 is responsible for degradation of cGMP. 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. Its effect is more potent on PDE5 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).

Drug Interactions for Revatio

There are risks to the mother and fetus from untreated pulmonary arterial hypertension (see Clinical Considerations). Animal reproduction studies conducted with sildenafil showed no evidence of embryo-fetal toxicity or teratogenicity at doses up to 32- and 65-times the recommended human dose (RHD) of 20 mg three times a day in rats and rabbits, respectively (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.

Less common

general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Disease-Associated Maternal And/Or Embryo/Fetal Risk Pregnant women with untreated pfizer sildenafil 50 pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death. 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 65-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). Limited published data from a case report describe the presence of sildenafil and its active metabolite in human milk. The approximately 4,000-fold selectivity for PDE-5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility.