Oral Sildenafil in the Treatment of Erectile Dysfunction

Sections or subsections omitted from the full prescribing information are not listed. 1 INDICATIONS AND USAGE AdultsSildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group I) in adults to improve exercise ability and delay clinical worsening [see Clinical Studies (14)] .Pediatric use information is approved for Viatris Specialty LLC’s, REVATIO (sildenafil) tablets. Sildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group I) in adults to improve exercise ability and delay clinical worsening [see Clinical Studies (14)] .

2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage in AdultsOral DosageThe recommended dosage of sildenafil tablet is 20 mg three times a day [see Clinical Studies (14)] .Pediatric use information is approved for Viatris Specialty LLC’s, REVATIO (sildenafil) tablets. The recommended dosage of sildenafil tablet is 20 mg three times a day [see Clinical Studies (14)] . 4 CONTRAINDICATIONS Sildenafil tablets are contraindicated in patients with:Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.1)] .Concomitant use of riociguat, a guanylate cyclase stimulator.

Further information

Sections or subsections omitted from the full prescribing information are not listed. 1 INDICATIONS AND USAGE AdultsSildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group I) in adults to improve exercise ability and delay clinical worsening [see Clinical Studies (14)] .Pediatric use information is approved for Viatris Specialty LLC’s, REVATIO (sildenafil) tablets. Sildenafil tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group I) in adults to improve exercise ability and delay clinical worsening [see Clinical Studies (14)] . 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage in AdultsOral DosageThe recommended dosage of sildenafil tablet is 20 mg three times a day [see Clinical Studies (14)] .Pediatric use information is approved for Viatris Specialty LLC’s, REVATIO (sildenafil) tablets. The recommended dosage of sildenafil tablet is 20 mg three times a day [see Clinical Studies (14)] .

Incidence not known

4 CONTRAINDICATIONS Sildenafil tablets are contraindicated in patients with:Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.1)] .Concomitant use of riociguat, a guanylate cyclase stimulator. Phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.Known hypersensitivity to sildenafil or any component of the tablet. Hypersensitivity, including anaphylactic reaction, anaphylactic shock and anaphylactoid reaction, has been reported in association with the use of sildenafil. Sildenafil tablets are contraindicated in patients with: Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.1)] . Phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat. Phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.Known hypersensitivity to sildenafil or any component of the tablet. Hypersensitivity, including anaphylactic reaction, anaphylactic shock and anaphylactoid reaction, has been reported in association with the use of sildenafil. Sildenafil tablets are contraindicated in patients with: Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension [see Warnings and Precautions (5.1)] .

Phosphodiesterase-5 (PDE-5) inhibitors, including sildenafil, may potentiate the hypotensive effects of riociguat.

Known hypersensitivity to sildenafil or any component of the tablet. 5 WARNINGS AND PRECAUTIONS 5.1 HypotensionSildenafil citrate has vasodilatory properties, resulting in mild and transient decreases in blood pressure. Before prescribing sildenafil citrate, 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 citrate.5.2 Worsening Pulmonary Vascular Occlusive DiseasePulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD).

Before taking this medicine

Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Should signs of pulmonary edema occur when sildenafil citrate is administered, consider the possibility of associated PVOD. The 200mg sildenafil citrate incidence of epistaxis was 13% in patients taking sildenafil citrate with PAH secondary to CTD. The incidence of epistaxis was also higher in sildenafil citrate-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 citrate is unknown in patients with bleeding disorders or active peptic ulceration.

Vybrique Oral Film

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 citrate. There are no controlled clinical data on the safety or efficacy of sildenafil citrate in patients with retinitis pigmentosa, a minority of whom have genetic disorders of retinal phosphodiesterases. Therefore, use of sildenafil citrate in patients with retinitis pigmentosa is not recommended. Since there are no clinical data on administration of sildenafil citrate to patients with veno-occlusive disease, administration of sildenafil citrate to such patients is not recommended. Should signs of pulmonary edema occur when sildenafil citrate is administered, consider the possibility of associated PVOD.5.3 EpistaxisThe incidence of sildenafil 50mg tablet epistaxis was 13% in patients taking sildenafil citrate with PAH secondary to CTD. This effect was not seen in idiopathic PAH (sildenafil citrate 3%, placebo 2%) patients. The incidence of epistaxis was also higher in sildenafil citrate-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 citrate is unknown in patients with bleeding disorders or active peptic ulceration.5.4 Visual LossWhen 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 citrate.There are no controlled clinical data on the safety or efficacy of sildenafil citrate in patients with retinitis pigmentosa, a minority of whom have genetic disorders of retinal phosphodiesterases. Therefore, use of sildenafil citrate in patients with retinitis pigmentosa is not recommended.5.5 Hearing LossCases 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 citrate.

• Sildenafil is a PDE5 inhibitor specifically designed to treat erectile dysfunction.
• Use sildenafil tablets only as prescribed; do not share your medication.
• Contact your doctor if you notice an allergic reaction, such as swelling or rash.

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.

Warnings & Precautions

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 citrate. It is not possible to determine whether these reported events are related directly to the use of sildenafil citrate, 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 citrate. Inform patients taking sildenafil citrate 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.

Other Interactions

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 citrate than by those randomized to placebo. 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)]6.1 Clinical Trials ExperienceBecause 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 citrate-treated adults with PAH (WHO Group I) [see Clinical Studies (14)] the adverse reactions that were reported by at least 10% of sildenafil citrate -treated patients in any dosing group, and were more frequent in sildenafil citrate -treated patients than in placebo-treated patients are shown in Table 1. It is not possible to determine whether these reported events are related directly to the use of sildenafil citrate, 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 citrate.5.6 Combination with other PDE-5 InhibitorsSildenafil is also marketed as VIAGRA ®. The safety and efficacy of combinations of sildenafil citrate with VIAGRA or other PDE-5 inhibitors have not been studied. Inform patients taking sildenafil citrate not to take VIAGRA or other PDE-5 inhibitors.5.7 PriapismUse sildenafil citrate 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 DiseaseIn 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 citrate than by those randomized to placebo.

Non-medical use

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 citrate, 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 citrate.5.6 Combination with other PDE-5 InhibitorsSildenafil is also marketed as VIAGRA ®. The safety and efficacy of combinations of sildenafil citrate with VIAGRA or other PDE-5 inhibitors have not been studied. Inform patients taking sildenafil citrate not to take VIAGRA or other PDE-5 inhibitors.5.7 PriapismUse sildenafil citrate 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).

Drugs Affecting Gastric Acidity

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 DiseaseIn 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 citrate than by those randomized to placebo. The effectiveness and safety of sildenafil citrate in the treatment of PH secondary to sickle cell disease has not been established. Sildenafil citrate has vasodilatory properties, resulting women sildenafil in mild and transient decreases in blood pressure. Monitor blood pressure when co-administering blood pressure lowering drugs with sildenafil citrate. The effectiveness and safety of sildenafil citrate in the treatment of PH secondary to sickle cell disease has not been established. Sildenafil citrate has vasodilatory properties, resulting women sildenafil in mild and transient decreases in blood pressure. Monitor blood pressure when co-administering blood pressure lowering drugs with sildenafil citrate. Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Should signs of pulmonary edema occur when sildenafil citrate is administered, consider the possibility of associated PVOD.

• Potential side effects of sildenafil tablets include headache, flushing, and nasal congestion.
• Serious side effects are rare but can include vision changes or prolonged erections.
• Seek medical attention if you experience chest pain or an erection lasting over 4 hours.

The 200mg sildenafil citrate incidence of epistaxis was 13% in patients taking sildenafil citrate with PAH secondary to CTD. The incidence of epistaxis was also higher in sildenafil citrate-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 citrate 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”). Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking sildenafil citrate. There are no controlled clinical data on the safety or efficacy of sildenafil citrate in patients with retinitis pigmentosa, a minority of whom have genetic disorders of retinal phosphodiesterases. Therefore, use of sildenafil citrate in patients with retinitis pigmentosa is not recommended.

In case of emergency/overdose

Known hypersensitivity to sildenafil or any component of the tablet. 5 WARNINGS AND PRECAUTIONS 5.1 HypotensionSildenafil citrate has vasodilatory properties, resulting in mild and transient decreases in blood pressure. Before prescribing sildenafil citrate, 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 citrate.5.2 Worsening Pulmonary Vascular Occlusive DiseasePulmonary 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 citrate to patients with veno-occlusive disease, administration of sildenafil citrate to such patients is not recommended.

Why it’s used

Should signs of pulmonary edema occur when sildenafil citrate is administered, consider the possibility of associated PVOD.5.3 EpistaxisThe incidence of sildenafil 50mg tablet epistaxis was 13% in patients taking sildenafil citrate with PAH secondary to CTD. This effect was not seen in idiopathic PAH (sildenafil citrate 3%, placebo 2%) patients. The incidence of epistaxis was also higher in sildenafil citrate-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 citrate is unknown in patients with bleeding disorders or active peptic ulceration.5.4 Visual LossWhen 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 citrate.There are no controlled clinical data on the safety or efficacy of sildenafil citrate in patients with retinitis pigmentosa, a minority of whom have genetic disorders of retinal phosphodiesterases. Therefore, use of sildenafil citrate in patients with retinitis pigmentosa is not recommended.5.5 Hearing LossCases 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 citrate. 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 citrate. It is not possible to determine whether these reported events are related directly to the use of sildenafil citrate, 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 citrate. Inform patients taking sildenafil citrate 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.

Mechanism of action

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

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 citrate than by those randomized to placebo. 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)]6.1 Clinical Trials ExperienceBecause 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 citrate-treated adults with PAH (WHO Group I) [see Clinical Studies (14)] the adverse reactions that were reported by at least 10% of sildenafil citrate -treated patients in any dosing group, and were more frequent in sildenafil citrate -treated patients than in placebo-treated patients are shown in Table 1.