11 DESCRIPTION

Food and Drug Administration Revised: February 2024 50 mg PO ~1 hr before sexual activity; however, may be taken anywhere from 30 min to 4 hr before sexual activity Maximum dosing frequency is

Before taking this medicine

Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking Sildenafil. These events may be accompanied by tinnitus and dizziness. Trademarks are the property of their respective owners. PATIENT PACKAGE INSERT Pharmacist Print Patient Information at: Patient Information has been approved by the U.S. Food and Drug Administration Revised: February 2024 This Patient Information has been approved by the U.S. once per day Based on effectiveness and toleration, may increase dose to maximum of 100 mg or decrease to 25 mg Indicated for treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group

I) to improve exercise ability and delay clinical worsening Revatio (PO), Liqrev: 20 mg PO TID; may titrate up to 80 mg TID, if required, based on symptoms and tolerability Revatio (IV): 10 mg IV bolus TID 10-mg IV predicted to provide pharmacologic effect equivalent to 10-mg oral dose Do not exceed recommended PO/IV dose Viagra, VibriqueSevere (eg, cirrhosis): Consider initial dose of 25 mg Severe (eg,

Medicine brands for Sildenafil

Inform patients of contraindication of sildenafil with regular and/or intermittent use of organic nitrates. Inform patients that sildenafil is also marketed as VIAGRA ®for erectile dysfunction. Advise patients taking sildenafil not to take 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 sildenafil. Such an event may be a sign of NAION. cirrhosis): Consider initial dose of 25 mg RevatioMild or moderate (Child-Pugh A or B): No dose adjustment requiredSevere (Child-Pugh C): Not studied Mild or moderate (Child-Pugh A or B): No dose adjustment required

• Patient support resources are available for those taking sildenafil.
• Many pharmaceutical manufacturers offer patient assistance programs.
• Non-profit organizations provide information and support for ED and PAH.
• The Pulmonary Hypertension Association offers resources for PAH patients.
• Urology care foundations provide educational materials on ED treatments.
• Online forums and support groups can offer peer support and shared experiences.
• Healthcare providers are the primary source for personalized medical advice.
• Pharmacists are an excellent resource for information on dosing and side effects.
• Mental health professionals can help address psychological aspects of ED.
• Cardiac rehabilitation may be recommended for some PAH patients.
• A multidisciplinary approach often yields the best patient outcomes.

Viagra, VibriqueMild or moderate (CrCl 30-80 mL/min): No dose adjustment requiredSevere (CrCl <30 mL/min): Consider initial dose of 25 mg Mild or moderate (CrCl 30-80 mL/min): No dose adjustment required Severe (CrCl <30 mL/min):

• The medication should be stored at room temperature between 15-30°C (59-86°F).
• Keep the tablets in their original container, tightly closed.
• Protect from light and moisture; avoid storing in bathrooms or near sinks.
• Do not use the medication if the packaging is torn or shows signs of tampering.
• Check the expiration date printed on the bottle or blister pack before use.
• Properly discard any medication that is outdated or no longer needed.
• Do not flush medications down the toilet or pour them into a drain.
• Consult a pharmacist or local waste disposal company for proper disposal methods.
• Many communities have drug take-back programs for safe disposal.
• Keeping old medication increases the risk of accidental ingestion or misuse.
• Safe storage and disposal protect children, pets, and the environment.

Consider initial dose of 25 mg RevatioAny severity, including severe (CrCl <30 mL/min): No dose adjustment required Any severity, including severe (CrCl <30 mL/min): No dose adjustment required Indicated in children aged 1-17

Usual Geriatric Dose for Erectile Dysfunction

Patients were randomized to receive placebo (n = 70) or sildenafil 20 mg (n = 69), 40 mg (n = 67) or 80 mg (n = 71) three times a day for a period of 12 weeks. The study population consisted of 25% men and 75% women with a mean age of 49 years (range: 18 to 81 years) and baseline 6- minute walk distance between 100 and 450 meters (mean 343). The primary efficacy endpoint was the change from baseline at Week 12 (at least 4 hours after the last dose) in the 6-minute walk distance. The improvement in walk distance was apparent after 4 weeks of treatment and was maintained at Week 8 and Week 12. Change from Baseline in 6-Minute Walk Distance (meters) at Weeks 4, 8, and 12 in SUPER-1: Mean (95% Confidence Interval) Figure 4 displays subgroup efficacy analyses in SUPER-1 for the change from baseline in 6- Minute Walk Distance at Week 12 including baseline walk distance, disease etiology, functional class, gender, age, and hemodynamic parameters.

Serious Side Effects

Placebo-Corrected Change From Baseline in 6-Minute Walk Distance (meters) at Week 12 by Study Subpopulation in SUPER-1: Mean (95% Confidence Interval) Key:PAH = pulmonary arterial hypertension; CTD = connective tissue disease; PH = pulmonary hypertension; PAP = pulmonary arterial pressure; PVRI = pulmonary vascular resistance index; TID = three times daily. SUPER-2 (NCT00159887) Long-term Treatment of PAH In a long-term follow-up of patients who were treated with sildenafil (n=277), K-M estimates of survival at 1, 2, and sildenafil 25 mg tablets 3 years were 94%, 88%, and 79%, respectively. These uncontrolled observations do not allow comparison with a group not given sildenafil and cannot be used to determine the long term-effect of sildenafil on mortality. PACES-1 (NCT00159861) - Sildenafil Co-administered with Epoprostenol A randomized, double-blind, placebo-controlled study (PACES-1) was conducted in 267 patients with PAH who were taking stable doses of intravenous epoprostenol. Patients had to have a mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg and a pulmonary capillary wedge pressure (PCWP) less than or equal to 15 mmHg at rest via right heart catheterization within 21 days before randomization, and a baseline 6-minute walk test distance greater than or equal to 100 meters and less than or equal to 450 meters (mean 349 meters). years for treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise ability and, in pediatric patients too young to perform standard exercise testing, pulmonary hemodynamics thought to underly improvements in exercise

14. Clinical Studies

Study A1481243 (NCT00323297) – Sildenafil Added to Bosentan Therapy – Lack of Effect on Exercise Capacity A randomized, double-blind, placebo-controlled study was conducted in 103 patients with PAH who were on bosentan therapy for a minimum of 3 months. The results indicate that there is no significant difference in mean change from baseline on 6MWD observed between sildenafil 20 mg plus bosentan and buy sildenafil uk bosentan alone. Pediatric use information is approved for Viatris Specialty LLC’s, REVATIO ®(sildenafil) tablets. 16 HOW SUPPLIED/STORAGE AND HANDLING Sildenafil Tablets, USP 20 mg are blue colored, round, film-coated tablets, debossed with “CE” on one side and “109” on the other side and are supplied in bottles of 90 tablets.Bottles of 90 NDC 62135-372-90Store atRecommended storage for sildenafil tablets: 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. Sildenafil Tablets, USP 20 mg are blue colored, round, film-coated tablets, debossed with “CE” on one side and “109” on the other side and are supplied in bottles of 90 tablets.

13.1 Carcinogenesis & Mutagenesis & Impairment of Fertility

Bottles of 90 NDC 62135-372-90 Recommended storage for sildenafil tablets: 20°-25°C (68°-77°F) [see USP Controlled Room Temperature]. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).Inform patients of contraindication of sildenafil with regular and/or intermittent use of organic nitrates.Inform patients that sildenafil is also marketed as VIAGRA ®for erectile dysfunction. Advise patients taking sildenafil not to take 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 sildenafil. 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 Sildenafil. These events may be accompanied by tinnitus and dizziness.Trademarks are the property of their respective owners.Manufactured for:Chartwell RX, LLCCongers, NY 10920L71823Revised 03/2024Pharmacist Print Patient Information at: Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). 20-45 kg: 20 mg PO TID Maximum dose in pediatric patients not identified Based on experience in adults, dose may be titrated up to 40 mg TID, if required, based on symptoms and tolerability Mild or moderate (Child-Pugh A or B): No dose adjustment required Any severity, including severe (CrCl <30 mL/min): No dose adjustment required ≥65 years: 25 mg PO initially ~1 hr before sexual activity;

• The societal impact of sildenafil has been profound since its introduction.
• It helped destigmatize the discussion and treatment of erectile dysfunction.
• It spawned a multi-billion dollar market for sexual health pharmaceuticals.
• The "Viagra" brand name became one of the most recognized in the world.
• It led to increased research and development in urology and sexual medicine.
• It also raised important questions about medicalization and lifestyle drugs.
• Direct-to-consumer advertising for ED treatments became widespread.
• It prompted debates about insurance coverage for quality-of-life medications.
• The success of sildenafil accelerated research into other PDE5 inhibitors.
• It highlighted the importance of serendipity in drug discovery.
• Its impact extends beyond medicine into cultural and social spheres.

however, may be taken anywhere from 30 min to 4 hr before sexual activity Maximum dosing frequency is once per day Based on effectiveness and toleration, may increase dose to maximum of 100 mg or decrease to 25 mg Indicated for treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group I) to improve exercise ability and delay clinical worsening PO: 20 mg PO TID; may

titrate up to 80 mg TID, if required , based on symptoms and tolerability 10-mg IV predicted to provide pharmacologic effect equivalent to 10-mg oral dose Recommended PO/IV dose not to be exceeded

Adding Revatio to bosentan does not have any beneficial effect on exercise capacity Clinical trials found no significant difference in response between elderly patients and younger adults; however, cautious dose selection should be considered

8.2 Lactation

Kaplan-Meier plot of time to clinical worsening is presented in Figure 5.Table 4. Clinical Worsening Events in PACES-1Figure 5. Kaplan-Meier Plot of Time (in Days) to Clinical Worsening of PAH in PACES-1Improvements in WHO Functional Class for PAH were also demonstrated in patients on sildenafil compared to placebo. More than twice as many sildenafil-treated patients (36%) as placebo-treated patients (14%) showed an improvement in at least one functional New York Heart Association (NYHA) class for PAH.Study A1481243 (NCT00323297) – Sildenafil Added to Bosentan Therapy – Lack of Effect on Exercise CapacityA randomized, double-blind, placebo-controlled study was conducted in 103 patients with PAH who were on bosentan therapy for a minimum of 3 months. The PAH patients included those with primary PAH and PAH associated with CTD.

Common Side Effects

Patients were randomized to placebo or sildenafil (20 mg three times a day) in combination with bosentan (62.5 to 125 mg twice a day). The primary efficacy endpoint was the change from baseline at Week 12 in 6-minute walk distance (6MWD). The results indicate that there is no significant difference in mean change from baseline on 6MWD observed between sildenafil 20 mg plus bosentan and bosentan alone.Pediatric use information is approved for Viatris Specialty LLC’s, REVATIO ®(sildenafil) tablets. SUPER-1 (NCT00644605) - Sildenafil monotherapy [20 mg, 40 mg, and 80 mg three times a day] A randomized, double-blind, placebo-controlled study of sildenafil (SUPER-1) was conducted in 277 patients with PAH (defined as a mean pulmonary artery pressure ≥25 mmHg at rest with a pulmonary capillary wedge pressure <15 mmHg). Patients with left ventricular ejection fraction less than 45% or left ventricular shortening fraction less than 0.2 also were not studied. in elderly because of greater frequency of decreased hepatic, renal, and cardiac function, as well as comorbid conditions and concomitant pharmacotherapy Compared with healthy younger volunteers, healthy elderly volunteers (≥65 years) had reduced clearance

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Patients were randomized to placebo or sildenafil (in a fixed titration starting from 20 mg to 40 mg and then 80 mg, three times a day) and all patients continued intravenous epoprostenol therapy. At baseline patients had PPH (80%) or PAH secondary to CTD (20%); WHO Functional Class I (1%), II (26%), III (67%), or IV (6%); and the mean age was 48 years, 80% were female, and 79% were Caucasian. There was a statistically significant greater increase from baseline in 6-minute walk distance at Week 16 (primary endpoint) for the sildenafil group compared with the placebo group. The mean change from baseline at Week 16 (last observation carried forward) was 30 meters for the sildenafil group compared with 4 meters for the placebo group giving an adjusted treatment difference of 26 meters (95% CI: 10.8, 41.2) (p = 0.0009). Patients on sildenafil achieved a statistically significant reduction in mPAP compared to those on placebo.

7.1 Nitrates

A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favor of sildenafil (95% CI: -5.7, -2.1) (p = 0.00003). Time to clinical worsening of PAH was defined as the time from randomization to the first occurrence of a clinical worsening event (death, lung transplantation, initiation of bosentan therapy, or clinical deterioration requiring a change in epoprostenol therapy). Kaplan-Meier plot of time to clinical worsening is presented in Figure 5. Kaplan-Meier Plot of Time (in Days) to Clinical Worsening of PAH in PACES-1 Improvements in WHO Functional Class for PAH were also demonstrated in patients on sildenafil compared to placebo. More than twice as many sildenafil-treated patients (36%) as placebo-treated patients (14%) showed an improvement in at least one functional New York Heart Association (NYHA) class for PAH. of sildenafil, resulting in approximately 84% and 107% higher plasma concentrations of sildenafil and its active N-desmethyl metabolite, respectively atazanaviratazanavir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism.