10 OVERDOSAGE

Patients were randomized to placebo or sildenafil citrate (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. The mean change from baseline at Week 16 (last observation carried forward) was 30 meters for the sildenafil tablet 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). A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favor of sildenafil tablet (95% CI: -5.7, -2.1) (p = 0.00003).

• Sildenafil tablets can cause a sudden drop in blood pressure if combined with nitrates.
• Proper hydration helps ensure the effectiveness of sildenafil tablets.
• Reading the patient information leaflet helps understand the correct use of sildenafil.

Kaplan- Meier plot of time to clinical worsening is presented in Figure 5.

Advice To Patients

Patients were randomized to placebo or sildenafil citrate (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. The mean change from baseline at Week 16 (last observation carried forward) was 30 meters for the sildenafil tablet 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). A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favor of sildenafil tablet (95% CI: -5.7, -2.1) (p = 0.00003). Kaplan- Meier plot of time to clinical worsening is presented in Figure 5.

Sildenafil Tablets or Oral Suspension for PAH

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 tablet compared to placebo. More than twice as many sildenafil citrate -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 citrate 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. STARTS-1 ( NCT00159913) - Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension A total of 234 patients with PAH aged 1 to 17 years were treated in a randomized, double-blind, multi-center, placebo-controlled parallel group, dose-ranging study. Patients were WHO Functional Class I (32%), II (51%), III (15%), or IV (0.4%).

Other Interactions

Patients were naïve for specific PAH therapy and the use of prostacyclin, prostacyclin analogues and endothelin receptor antagonists were not permitted in the study, and neither were arginine supplementation, nitrates, alpha-blockers and potent CYP450 3A4 inhibitors. The primary objective of the study was to assess the effect of Sildenafil citrate on percent change from baseline in PVO2, normalized to body weight, from baseline to week 16 as measured by the Cardiopulmonary Exercise Test (CPET) (patients who were developmentally able to perform the test, n = 115). Secondary endpoints included hemodynamic monitoring, symptom assessment, WHO Functional Class, change in background treatment, and quality of life measurements (n sildenafil 200 mg = 234). Patients were allocated to one of three sildenafil treatment groups (low, medium, or high) or placebo. Actual doses administered were dependent on body weight (see Table 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 tablet compared to placebo. More than twice as many sildenafil citrate -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 citrate 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. STARTS-1 ( NCT00159913) - Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension A total of 234 patients with PAH aged 1 to 17 years were treated in a randomized, double-blind, multi-center, placebo-controlled parallel group, dose-ranging study.

Patients were WHO Functional Class I (32%), II (51%), III (15%), or IV (0.4%).

Route of administration

The proportion of patients receiving supportive medicinal products at baseline (anticoagulants, digoxin, calcium channel blockers, diuretics and/or oxygen) was similar in the combined sildenafil treatment group (48%) and the placebo treatment group (42%). The primary endpoint was a percentage change in VO2peak from baseline to week 16 assessed by CPET. A total of 45% of patients were evaluable for CPET, which comprised those children ≥7 years old and developmentally able to perform the test. Children <7 years were evaluable only for the secondary endpoints. Mean increases in VO 2peakpercentage change from baseline at Week 16, were observed with all 3 sildenafil doses (range of 6% to 13%, Figure 6), with little change with placebo (0.5%).

Therapies for Erectile Dysfunction

Percentage Change from Baseline in VO2Peak: Mean (95% Confidence Intervals) The estimated difference between the combined sildenafil doses and placebo was 8% (95% CI: 0.2 to 16). The results of the main analysis (combined dose groups versus placebo) were not statistically significant (p=0.056). The estimated difference between the sildenafil medium dose group and placebo was 11±5% (95% CI: 2 to 21). STARTS-2 ( NCT00159874) - Long-Term Survival with Oral Sildenafil Monotherapy in Treatment-Naïve Pediatric Pulmonary Arterial Hypertension Of the 234 pediatric patients treated in the short-term, placebo-controlled study, 220 patients entered the long-term extension study. By sildenafil treatment group, median duration of sildenafil treatment was 1,696 days (excluding the 5 patients who received placebo in double-blind and were not treated in the long-term extension study).

Sildenafil Oral Film for ED

Peak VO 2was assessed 1 year after the start of the placebo-controlled study. Similarly, 191 of 229 patients (83%) who had received sildenafil had either maintained or improved their WHO Functional sildenafil 60mg Class at 1 year assessment. Kaplan-Meier estimates of survival at 3 years in patients >20 kg in weight at baseline were 94%, 93%, and 85% in the low, medium, and high dose groups, respectively; for patients ≤20 kg in weight at baseline, the survival estimates were 94% and 93% for patients in the medium and high dose groups, respectively [ see Use in Specific Populations ( 8.4) and Adverse Reactions ( 6.1) ]. Study A1481324 ( NCT02060487) - Study to Assess the Effects of Sildenafil citrate on Mortality in Adults with PAH A study to assess the effects of multiple doses of sildenafil on mortality in adults with PAH was conducted following the observation of a higher risk of mortality in pediatric patients taking a high dose of Sildenafil citrate TID, based on body weight, compared to those taking a lower dose of Sildenafil citrate in the long-term extension of the pediatric clinical trial. The study was a randomized, double-blind, parallel-group study in 385 adults with PAH. Patients were naïve for specific PAH therapy and the use of prostacyclin, prostacyclin analogues and endothelin receptor antagonists were not permitted in the study, and neither were arginine supplementation, nitrates, alpha-blockers and potent CYP450 3A4 inhibitors. The primary objective of the study was to assess the effect of Sildenafil citrate on percent change from baseline in PVO2, normalized to body weight, from baseline to week 16 as measured by the Cardiopulmonary Exercise Test (CPET) (patients who were developmentally able to perform the test, n = 115). Secondary endpoints included hemodynamic monitoring, symptom assessment, WHO Functional Class, change in background treatment, and quality of life measurements (n sildenafil 200 mg = 234). Patients were allocated to one of three sildenafil treatment groups (low, medium, or high) or placebo. Actual doses administered were dependent on body weight (see Table 5). The proportion of patients receiving supportive medicinal products at baseline (anticoagulants, digoxin, calcium channel blockers, diuretics and/or oxygen) was similar in the combined sildenafil treatment group (48%) and the placebo treatment group (42%).

• Sildenafil tablets are used to treat erectile dysfunction by improving blood flow to the penis.
• Common dosages of sildenafil tablets include 25mg, 50mg, and 100mg.
• Always follow a healthcare provider’s instructions when taking sildenafil tablets.

The primary endpoint was a percentage change in VO2peak from baseline to week 16 assessed by CPET. A total of 45% of patients were evaluable for CPET, which comprised those children ≥7 years old and developmentally able to perform the test. Children <7 years were evaluable only for the secondary endpoints. Mean increases in VO 2peakpercentage change from baseline at Week 16, were observed with all 3 sildenafil doses (range of 6% to 13%, Figure 6), with little change with placebo (0.5%). Percentage Change from Baseline in VO2Peak: Mean (95% Confidence Intervals) The estimated difference between the combined sildenafil doses and placebo was 8% (95% CI: 0.2 to 16). The results of the main analysis (combined dose groups versus placebo) were not statistically significant (p=0.056). The estimated difference between the sildenafil medium dose group and placebo was 11±5% (95% CI: 2 to 21). STARTS-2 ( NCT00159874) - Long-Term Survival with Oral Sildenafil Monotherapy in Treatment-Naïve Pediatric Pulmonary Arterial Hypertension Of the 234 pediatric patients treated in the short-term, placebo-controlled study, 220 patients entered the long-term extension study. By sildenafil treatment group, median duration of sildenafil treatment was 1,696 days (excluding the 5 patients who received placebo in double-blind and were not treated in the long-term extension study). Peak VO 2was assessed 1 year after the start of the placebo-controlled study. Similarly, 191 of 229 patients (83%) who had received sildenafil had either maintained or improved their WHO Functional sildenafil 60mg Class at 1 year assessment. Kaplan-Meier estimates of survival at 3 years in patients >20 kg in weight at baseline were 94%, 93%, and 85% in the low, medium, and high dose groups, respectively; for patients ≤20 kg in weight at baseline, the survival estimates were 94% and 93% for patients in the medium and high dose groups, respectively [ see Use in Specific Populations ( 8.4) and Adverse Reactions ( 6.1) ].

5.7 Priapism

• Inform patients of contraindication of sildenafil tablets 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 tablets 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 tablets. • Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking sildenafil tablets.

Other Medical Problems

Trademarks are the property of their respective owners. First of all, thank you for choosing Numan.

A note about sex and gender

Study A1481324 ( NCT02060487) - Study to Assess the Effects of Sildenafil citrate on Mortality in Adults with PAH A study to assess the effects of multiple doses of sildenafil on mortality in adults with PAH was conducted following the observation of a higher risk of mortality in pediatric patients taking a high dose of Sildenafil citrate TID, based on body weight, compared to those taking a lower dose of Sildenafil citrate in the long-term extension of the pediatric clinical trial. The study was a randomized, double-blind, parallel-group study in 385 adults with PAH. Treatment groups were well balanced with respect to baseline demographics of strata history of PAH treatment and etiology of PAH, as well as the WHO Functional Class categories.

What should I know about storage and disposal of this medication?

Treatment groups were well balanced with respect to baseline demographics of strata history of PAH treatment and etiology of PAH, as well as the WHO Functional Class categories. The primary objective of the study was to compare sildenafil 80 mg TID versus 5 mg TID for mortality, with success defined by ruling out twice the mortality at 80 mg. The key secondary efficacy endpoint was time to first event of clinical worsening, defined as a composite endpoint of all-cause mortality, hospitalization for worsening PAH or disease progression. An additional secondary endpoint was 6MWD at Months 6 and 12. Kaplan-Meier estimates of survival at 3 years were 66%, 79%, and 85% in the 5-, 20-, and 80mg TID dose groups, respectively At baseline, the median of 6MWD for the intent-to-treat (ITT) population was 332 to 352 m.

Why it’s used

At Month 6, the median change from baseline was highest for sildenafil 80 mg TID with 28 m compared to 18 m and 19 m for sildenafil 5 mg TID and sildenafil 20 mg TID groups, respectively. The same was seen at Month 12, the median change from baseline for sildenafil 80 mg TID group was buy sildenafil citrate online canada 33 m compared to 17 m for sildenafil 5 mg TID and 31 m in sildenafil 20 mg TID groups. Overall, the safety data for sildenafil 20 mg TID and for the higher sildenafil 80 mg TID dose were consistent with the established safety profile of sildenafil in previous adult PAH studies [ see Adverse Reactions ( 6.1) ]. 16 HOW SUPPLIED/STORAGE AND HANDLING Sildenafil 20 mg tablets USP are white to off-white, round biconvex film coated tablets debossed with '85' on one side and plain on other side.Bottles of 30 with child-resistant closure NDC 76420-613-30 (repackaged from NDC 13668-185-xx)Bottles of 60 with child-resistant closure NDC 76420-613-60 (repackaged from NDC 13668-185-xx)Bottles of 90 with child-resistant closure NDC 76420-613-90 (relabeled/repackaged from NDC 13668-185-90/NDC 13668-185-xx)Recommended Storage for Sildenafil Tablets USP: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Sildenafil 20 mg tablets USP are white to off-white, round biconvex film coated tablets debossed with '85' on one side and plain on other side.

Altitude sickness

Bottles of 30 with child-resistant closure NDC 76420-613-30 (repackaged from NDC 13668-185-xx) Bottles of 60 with child-resistant closure NDC 76420-613-60 (repackaged from NDC 13668-185-xx) Bottles of 90 with child-resistant closure NDC 76420-613-90 (relabeled/repackaged from NDC 13668-185-90/NDC 13668-185-xx) Recommended Storage for Sildenafil Tablets USP: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).• Inform patients of contraindication of sildenafil tablets 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 tablets 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 tablets. 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 tablets. These events may be accompanied by tinnitus and dizziness.Trademarks are the property of their respective owners.Relabeled and Repackaged by:Enovachem PHARMACEUTICALSTorrance, CA 90501 Advise the patient to read the FDA-approved patient labeling (Patient Information). The primary objective of the study was to compare sildenafil 80 mg TID versus 5 mg TID for mortality, with success defined by ruling out twice the mortality at 80 mg. The key secondary efficacy endpoint was time to first event of clinical worsening, defined as a composite endpoint of all-cause mortality, hospitalization for worsening PAH or disease progression. An additional secondary endpoint was 6MWD at Months 6 and 12. Kaplan-Meier estimates of survival at 3 years were 66%, 79%, and 85% in the 5-, 20-, and 80mg TID dose groups, respectively At baseline, the median of 6MWD for the intent-to-treat (ITT) population was 332 to 352 m. At Month 6, the median change from baseline was highest for sildenafil 80 mg TID with 28 m compared to 18 m and 19 m for sildenafil 5 mg TID and sildenafil 20 mg TID groups, respectively. The same was seen at Month 12, the median change from baseline for sildenafil 80 mg TID group was buy sildenafil citrate online canada 33 m compared to 17 m for sildenafil 5 mg TID and 31 m in sildenafil 20 mg TID groups. Overall, the safety data for sildenafil 20 mg TID and for the higher sildenafil 80 mg TID dose were consistent with the established safety profile of sildenafil in previous adult PAH studies [ see Adverse Reactions ( 6.1) ]. 16 HOW SUPPLIED/STORAGE AND HANDLING Sildenafil 20 mg tablets USP are white to off-white, round biconvex film coated tablets debossed with '85' on one side and plain on other side.Bottles of 30 with child-resistant closure NDC 76420-613-30 (repackaged from NDC 13668-185-xx)Bottles of 60 with child-resistant closure NDC 76420-613-60 (repackaged from NDC 13668-185-xx)Bottles of 90 with child-resistant closure NDC 76420-613-90 (relabeled/repackaged from NDC 13668-185-90/NDC 13668-185-xx)Recommended Storage for Sildenafil Tablets USP: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Sildenafil 20 mg tablets USP are white to off-white, round biconvex film coated tablets debossed with '85' on one side and plain on other side. Bottles of 30 with child-resistant closure NDC 76420-613-30 (repackaged from NDC 13668-185-xx) Bottles of 60 with child-resistant closure NDC 76420-613-60 (repackaged from NDC 13668-185-xx) Bottles of 90 with child-resistant closure NDC 76420-613-90 (relabeled/repackaged from NDC 13668-185-90/NDC 13668-185-xx) Recommended Storage for Sildenafil Tablets USP: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).• Inform patients of contraindication of sildenafil tablets 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 tablets 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 tablets. 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 tablets. These events may be accompanied by tinnitus and dizziness.Trademarks are the property of their respective owners.Relabeled and Repackaged by:Enovachem PHARMACEUTICALSTorrance, CA 90501 Advise the patient to read the FDA-approved patient labeling (Patient Information). • Inform patients of contraindication of sildenafil tablets 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 tablets 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 tablets. • Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking sildenafil tablets. Trademarks are the property of their respective owners. First of all, thank you for choosing Numan.