FDA label 3b5210ff-e537-ea3b-e063-6394a90aaebe

5 WARNINGS AND PRECAUTIONS Vasodilation effects may be more common in patients with hypotension or on antihypertensive therapy. ( 5.1 ) Use in pulmonary veno-occlusive disease (PVOD) may cause pulmonary edema and is not recommended. ( 5.2 ) Hearing or visual impairment: Seek medical attention if sudden decrease or loss of vision or hearing occurs. ( 5.4 , 5.5 ) Pulmonary hypertension (PH) secondary to sickle cell disease: Sildenafil may cause serious vaso-occlusive crises. ( 5.8 ) 5.1 Hypotension Sildenafil has vasodilatory properties, resulting in mild and transient decreases in blood pressure. Before prescribing Sildenafil for Oral Suspension, carefully consider whether patients with certain underlying conditions could be adversely affected by such vasodilatory effects (e.g., patients on antihypertensive therapy or with resting hypotension [blood pressure less than 90/50], fluid depletion, severe left ventricular outflow obstruction, or autonomic dysfunction). Monitor blood pressure when co-administering blood pressure lowering drugs with Sildenafil for Oral Suspension. 5.2 Worsening Pulmonary Vascular Occlusive Disease Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Since there are no clinical data on administration of Sildenafil for Oral Suspension to patients with veno-occlusive disease, administration of Sildenafil for Oral Suspension to such patients is not recommended. Should signs of pulmonary edema occur when Sildenafil for Oral Suspension is administered, consider the possibility of associated PVOD. 5.3 Epistaxis The incidence of epistaxis was 13% in patients taking Sildenafil for Oral Suspension with PAH secondary to CTD. This effect was not seen in idiopathic PAH (sildenafil 3%, placebo 2%) patients. The incidence of epistaxis was also higher in Sildenafil for Oral Suspension-treated patients with a concomitant oral vitamin K antagonist (9% versus 2% in those not treated with concomitant vitamin K antagonist). The safety of Sildenafil for Oral Suspension is unknown in patients with bleeding disorders or active peptic ulceration. 5.4 Visual Loss 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"). Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking Sildenafil for Oral Suspension. There are no controlled clinical data on the safety or efficacy of Sildenafil for Oral Suspension in patients with retinitis pigmentosa, a minority of whom have genetic disorders of retinal phosphodiesterases. Therefore, use of sildenafil in patients with retinitis pigmentosa is not recommended. 5.5 Hearing Loss 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 sildenafil. In some of the cases, medical conditions and other factors were reported that may have played a role. 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 Sildenafil for Oral Suspension, 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 Sildenafil for Oral Suspension. 5.6 Combination with Other PDE-5 inhibitors Sildenafil is also marketed as VIAGRA ® . The safety and efficacy of combinations of Sildenafil for Oral Suspension with VIAGRA or other PDE-5 inhibitors have not been studied. Inform patients taking Sildenafil for Oral Suspension not to take VIAGRA or other PDE-5 inhibitors. 5.7 Priapism Use Sildenafil for Oral Suspension with caution in patients with anatomical deformation of the penis (e.g., angulation, cavernosal fibrosis, or Peyronie's disease) or in patients who have conditions, which may predispose them to priapism (e.g., sickle cell anemia, multiple myeloma, or leukemia). In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism (painful erection greater than 6 hours in duration) is not treated immediately, penile tissue damage and permanent loss of potency could result. 5.8 Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell Disease 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 Sildenafil for Oral Suspension than by those randomized to placebo. The effectiveness and safety of Sildenafil for Oral Suspension in the treatment of PH secondary to sickle cell disease has not been established.

6 ADVERSE REACTIONS The following serious adverse events are discussed elsewhere in the labeling: Hypotension [see Warnings and Precautions (5.1) ] Vision Loss [see Warnings and Precautions (5.4) ] Hearing Loss [see Warnings and Precautions (5.5) ] Priapism [see Warnings and Precautions (5.7) ] Vaso-occlusive Crisis in Patients with Pulmonary Hypertension Secondary to Sickle Cell Disease [see Warnings and Precautions (5.8) ] Adults: Headache, dyspepsia, flushing, pain in limb, myalgia, back pain and diarrhea. ( 6.1 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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 practice. In a 12-week, placebo-controlled clinical study and an open-label extension study (SUPER-1) in 277 sildenafil-treated adults with PAH (WHO Group I) [see Clinical Studies (14) ] the adverse reactions that were reported by at least 10% of sildenafil-treated patients in any dosing group, and were more frequent in sildenafil-treated patients than in placebo-treated patients are shown in Table 1. Adverse reactions were generally transient and mild to moderate in nature. The overall frequency of discontinuation in sildenafil-treated patients was 3% (20 mg and 40 mg three times a day) and 8% (80 mg three times a day). The overall frequency of discontinuation for placebo was 3%. Table 1. Most Common Adverse Reactions in Patients Treated with Sildenafil 20 mg, 40 mg, 80 mg and Placebo three times per day in SUPER-1 (More Frequent in Sildenafil-Treated Patients than Placebo-Treated Patients) Sildenafil 20 mg Sildenafil 40 mg Sildenafil 80 mg Placebo (n = 69) (n = 67) (n = 71) (n = 70) Headache 46% 42% 49% 39% Flushing 10% 9% 16% 4% Pain in Limb 7% 15% 9% 6% Myalgia 7% 6% 14% 4% Back Pain 13% 13% 9% 11% Dyspepsia 13% 8% 13% 7% Diarrhea 9% 12% 10% 6% In a placebo-controlled fixed dose titration study (PACES-1) of sildenafil (starting with recommended dose of 20 mg and increased to 40 mg and then 80 mg all three times a day) as an adjunct to intravenous epoprostenol in patients with PAH, no new safety issues were identified except for edema, which occurred in 25% of subjects in the combined sildenafil + epoprostenol group compared with 13% of subjects in the epoprostenol group [see Clinical Studies (14) ] . Pediatric use information is approved for Viatris Specialty LLC's REVATIO ® (sildenafil) product. However, due to Viatris Specialty LLC's marketing exclusivity rights, this drug product is not labeled with that information. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of sildenafil (marketed for both PAH and erectile dysfunction). 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. Cardiovascular Events 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. 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. Nervous System Seizure, seizure recurrence Ophthalmologic NAION [see Warnings and Precautions (5.4) , Patient Counseling Information (17) ] .

<table width="100%"><caption>Table 1. Most Common Adverse Reactions in Patients Treated with Sildenafil 20 mg, 40 mg, 80 mg and Placebo three times per day in SUPER-1 (More Frequent in Sildenafil-Treated Patients than Placebo-Treated Patients)</caption><col align="left" valign="top" width="20%"/><col align="center" valign="top" width="20%"/><col align="center" valign="top" width="20%"/><col align="center" valign="top" width="20%"/><col align="center" valign="top" width="20%"/><thead><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">Sildenafil 20 mg </th><th styleCode="Rrule">Sildenafil 40 mg </th><th styleCode="Rrule">Sildenafil 80 mg </th><th styleCode="Rrule">Placebo</th></tr><tr><th styleCode="Lrule Rrule"/><th styleCode="Rrule">(n = 69)</th><th styleCode="Rrule">(n = 67)</th><th styleCode="Rrule">(n = 71)</th><th styleCode="Rrule">(n = 70)</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache</td><td styleCode="Rrule">46%</td><td styleCode="Rrule">42%</td><td styleCode="Rrule">49%</td><td styleCode="Rrule">39%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Flushing</td><td styleCode="Rrule">10%</td><td styleCode="Rrule">9%</td><td styleCode="Rrule">16%</td><td styleCode="Rrule">4%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Pain in Limb</td><td styleCode="Rrule">7%</td><td styleCode="Rrule">15%</td><td styleCode="Rrule">9%</td><td styleCode="Rrule">6%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Myalgia</td><td styleCode="Rrule">7%</td><td styleCode="Rrule">6%</td><td styleCode="Rrule">14%</td><td styleCode="Rrule">4%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Back Pain</td><td styleCode="Rrule">13%</td><td styleCode="Rrule">13%</td><td styleCode="Rrule">9%</td><td styleCode="Rrule">11%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Dyspepsia</td><td styleCode="Rrule">13%</td><td styleCode="Rrule">8%</td><td styleCode="Rrule">13%</td><td styleCode="Rrule">7%</td></tr><tr><td styleCode="Lrule Rrule">Diarrhea</td><td styleCode="Rrule">9%</td><td styleCode="Rrule">12%</td><td styleCode="Rrule">10%</td><td styleCode="Rrule">6%</td></tr></tbody></table>