13. NONCLINICAL TOXICOLOGY

12. Sildenafil Tablets - Clinical Pharmacology
5.6 Combination with other PDE-5 Inhibitors
Do you take the different doses in the same way?
Before Using
5.7 Combination with other PDE-5 inhibitors
52% of men experience some kind of erectile dysfunction throughout their life
What to do if viagra or sildenafil doesn’t work for you?

The study population consisted of 25% men and 75% women with a mean age of 49 years (range: 18–81 years) and baseline 6-minute walk distance between 100 and 450 meters (mean 343).

Sildenafil 20 mg tablets should be taken about 30 to 60 minutes before sexual activity.
It’s important not to take more than one dose in 24 hours.
Do not crush or chew the medication; swallow it whole with water.

Change from Baseline in 6-Minute Walk Distance (meters) at Weeks 4, 8, and 12 in Study 1: Mean (95% Confidence Interval) Figure 10 displays subgroup efficacy analyses in Study 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.

12. Sildenafil Tablets - Clinical Pharmacology

Why this range helps:

Placebo-Corrected Change From Baseline in 6-Minute Walk Distance (meters) at Week 12 by study subpopulation in Study 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. Study 2 (Sildenafil tablets co-administered with epoprostenol) A randomized, double-blind, placebo controlled study (Study 2) was conducted in 267 patients with PAH who were taking stable doses of intravenous epoprostenol.

Product	Dosage	Quantity + Bonus	Price
Viagra Generic	100mg	30 + 4 Pills	60.91€ 58.01€
Viagra Generic	25mg	360 + 10 Pills	213.68€ 203.50€
Viagra Generic	25mg	20 Pills	37.74€ 35.94€
Viagra Generic	50mg	30 + 4 Pills	54.26€ 51.68€
Kamagra	100mg	20 Pills	86.09€ 81.99€
Viagra Generic	100mg	120 + 6 Pills	149.50€ 142.38€
Viagra Generic	200mg	120 + 8 Pills	204.80€ 195.05€
Kamagra Oral Jelly	100mg	220 + 18 Sachets	662.24€ 630.70€
Viagra Generic	50mg	10 Pills	26.87€ 25.59€
Viagra Generic	150mg	30 + 2 Pills	72.32€ 68.88€
Viagra Generic	150mg	10 Pills	36.73€ 34.98€
Kamagra Oral Jelly	100mg	21 Sachets	95.92€ 91.35€
Viagra Generic	25mg	30 + 4 Pills	47.97€ 45.69€
Viagra Generic	25mg	270 + 8 Pills	184.26€ 175.49€

Patients were randomized to placebo or sildenafil tablets (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. There was a statistically significant greater increase from baseline in 6-minute walk distance at Week 16 (primary endpoint) for the sildenafil tablets group compared with the placebo group. The mean change from baseline at Week 16 (last observation carried forward) was 30 meters for the sildenafil tablets 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 tablets achieved a statistically significant reduction in mPAP compared to those on placebo. A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favor of sildenafil tablets (95% CI: -5.7, -2.1) (p = 0.00003).

5.6 Combination with other PDE-5 Inhibitors

See " What is the most important information I should know about Sildenafil tablets? "are allergic to sildenafil or any other ingredient in sildenafil tablets. See " What are the ingredients in sildenafil tablets? "at the end of this leaflet.What should I tell my doctor before taking sildenafil tablets?Tell your doctor about all of your medical conditions, including if youhave heart problems such as angina (chest pain), heart failure, irregular heartbeats, or have had a heart attackhave a disease called pulmonary veno-occlusive disease (PVOD)have high or low blood pressure or blood circulation problemshave an eye problem called retinitis pigmentosahave or had loss of sight in one or both eyeshave any problem with the shape of your penis or Peyronie's diseasehave any blood cell problems such sickle cell anemiahave a stomach ulcer or any bleeding problemsare pregnant or planning to become pregnant. Sildenafil passes into your breast milk or if it could harm your baby.Tell your doctor about all of the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal products.Sildenafil tablets and certain other medicines can cause side effects if you take them together.

Common Side Effects

"Ritonavir (Norvir ®) or other medicines used to treat HIV infectionKetoconazole (Nizoral ®)Itraconazole (Sporanox)High blood pressure medicineKnow the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.How should I take sildenafil tablets?Take sildenafil tablets exactly as your doctor tells you.Sildenafil tablets may be prescribed to you asSildenafil tabletsTake sildenafil tablets 3 times a day about 4 to 6 hours apart.Take sildenafil tablets at the same times every day.If you miss a dose, take it as soon as you remember. Talk to your doctor first.If you take too much sildenafil tablets, call your doctor or go to the nearest hospital emergency room.What are the possible side effects of sildenafil tablets?low blood pressure.Low blood pressure may cause you to feel faint or dizzy. Lie down if you feel faint or dizzy.more shortness of breath than usual.Tell your doctor if you get more short of breath after you start sildenafil tablets. More shortness of breath than usual may be due to your underlying medical condition.decreased eyesight or loss of sight in one or both eyes (NAION).If you notice a sudden decrease or loss of eyesight, talk to your doctor right away.sudden decrease or loss of hearing.If you notice a sudden decrease or loss of hearing, talk to your doctor right away. Kaplan-Meier Plot of Time (in Days) to Clinical Worsening of PAH (in Study 2) Improvements in WHO functional class for PAH were also demonstrated in subjects on sildenafil tablets compared to placebo.

Do you take the different doses in the same way?

Alcohol can interact with sildenafil, reducing its effectiveness and increasing side effects.
Avoid alcohol consumption when planning to use sildenafil.
Always inform your doctor about alcohol use prior to prescription.

Study 3 (Sildenafil tablets monotherapy (1 mg, 5 mg, and 20 mg three times a day)) A randomized, double-blind, parallel dose study (Study 3) was planned in 219 patients with PAH. Patients were randomized to 1 of 3 doses of Sildenafil tablets: 1 mg, 5 mg, and 20 mg, three times a day. At baseline patients had PPH (74%) or secondary PAH (26%); WHO functional class II (57%), III (41%), or IV (2%); the mean age was 44 years; and 67% were female. The majority of subjects were Asian (67%), and 28% were Caucasian. These increases were significantly better than those observed in the 1 mg dose group (Figure 12). Mean Change from Baseline in Six Minute Walk (meters) by Visit to Week 12 - ITT Population Sildenafil Protocol A1481244 Study 4 (Sildenafil Tablets 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 three months. HOW SUPPLIED/STORAGE AND HANDLING Sildenafil Tablets, USP 20 mg are supplied as white round, biconvex film coated tablets debossed with "R" on one side and "20" on the other side, containing sildenafil citrate equivalent to the nominally indicated amount of sildenafil as follows:Recommended Storage for Sildenafil Tablets, USP: Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature]. Sildenafil Tablets, USP 20 mg are supplied as white round, biconvex film coated tablets debossed with "R" on one side and "20" on the other side, containing sildenafil citrate equivalent to the nominally indicated amount of sildenafil as follows: Recommended Storage for Sildenafil Tablets, USP: Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature]. PATIENT COUNSELING INFORMATION See 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 tablets 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.

Before Using

The study population consisted of 25% men and 75% women with a mean age of 49 years (range: 18–81 years) and baseline 6-minute walk distance between 100 and 450 meters (mean 343). Change from Baseline in 6-Minute Walk Distance (meters) at Weeks 4, 8, and 12 in Study 1: Mean (95% Confidence Interval) Figure 10 displays subgroup efficacy analyses in Study 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. Placebo-Corrected Change From Baseline in 6-Minute Walk Distance (meters) at Week 12 by study subpopulation in Study 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. Study 2 (Sildenafil tablets co-administered with epoprostenol) A randomized, double-blind, placebo controlled study (Study 2) was conducted in 267 patients with PAH who were taking stable doses of intravenous epoprostenol. Patients were randomized to placebo or sildenafil tablets (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.

Dosage Forms and Strengths

There was a statistically significant greater increase from baseline in 6-minute walk distance at Week 16 (primary endpoint) for the sildenafil tablets group compared with the placebo group. The mean change from baseline at Week 16 (last observation carried forward) was 30 meters for the sildenafil tablets 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 tablets achieved a statistically significant reduction in mPAP compared to those on placebo. A mean placebo-corrected treatment effect of -3.9 mmHg was observed in favor of sildenafil tablets (95% CI: -5.7, -2.1) (p = 0.00003). Kaplan-Meier Plot of Time (in Days) to Clinical Worsening of PAH (in Study 2) Improvements in WHO functional class for PAH were also demonstrated in subjects on sildenafil tablets compared to placebo. 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. Inform patients of contraindication of sildenafil tablets with regular and/or intermittent use of organic nitrates. Inform patients that sildenafil tablets is also marketed as VIAGRA for erectile dysfunction. Advise patients taking sildenafil tablets not to take VIAGRA or other PDE-5 inhibitors.

Common side effects of sildenafil include headaches, flushing, and nasal congestion.
Serious side effects are rare but require immediate medical attention.
Patients should report any adverse reactions to their healthcare provider.

5.7 Combination with other PDE-5 inhibitors

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. Inform patients of contraindication of sildenafil tablets with regular and/or intermittent use of organic nitrates. Inform patients that sildenafil tablets is also marketed as VIAGRA for erectile dysfunction. Advise patients taking sildenafil tablets not to take VIAGRA or other PDE-5 inhibitors.

5.4 Hearing Loss

Advise patients over the counter drugs containing sildenafil 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. PATIENT PACKAGE INSERT Sildenafil (sil-DEN-a-fil) TabletsRead this Patient Information before you start taking sildenafil tablets and each time you get a refill. Your blood pressure could drop quickly to an unsafe level.Nitrate medicines include:Medicines that treat chest pain (angina)Nitroglycerin in any form including tablets, patches, sprays, and ointmentsIsosorbide mononitrate or dinitrateStreet drugs called "poppers" (amyl nitrate or nitrite)Guanylate cyclase stimulators include:Riociguat (Adempas)Ask your doctor or pharmacist if you are not sure if you are taking a nitrate or a guanylate cyclase stimulator medicine.What are sildenafil tablets?Sildenafil tablets are prescription medicine used in adults to treat pulmonary arterial hypertension (PAH). Your heart has to work hard to pump blood into your lungs.Sildenafil tablets improves the ability to exercise and can slow down worsening changes in your physical condition.Sildenafil tablets are not for use in childrenAdding sildenafil tablets to another medication used to treat PAH, bosentan (Tracleer®), does not result in improvement in your ability to exercise.Sildenafil tablets contain the same medicine as VIAGRA ®(sildenafil), which is used to treat erectile dysfunction (impotence). PATIENT PACKAGE INSERT Sildenafil (sil-DEN-a-fil) TabletsRead this Patient Information before you start taking sildenafil tablets and each time you get a refill. Your blood pressure could drop quickly to an unsafe level.Nitrate medicines include:Medicines that treat chest pain (angina)Nitroglycerin in any form including tablets, patches, sprays, and ointmentsIsosorbide mononitrate or dinitrateStreet drugs called "poppers" (amyl nitrate or nitrite)Guanylate cyclase stimulators include:Riociguat (Adempas)Ask your doctor or pharmacist if you are not sure if you are taking a nitrate or a guanylate cyclase stimulator medicine.What are sildenafil tablets?Sildenafil tablets are prescription medicine used in adults to treat pulmonary arterial hypertension (PAH). Your heart has to work hard to pump blood into your lungs.Sildenafil tablets improves the ability to exercise and can slow down worsening changes in your physical condition.Sildenafil tablets are not for use in childrenAdding sildenafil tablets to another medication used to treat PAH, bosentan (Tracleer®), does not result in improvement in your ability to exercise.Sildenafil tablets contain the same medicine as VIAGRA ®(sildenafil), which is used to treat erectile dysfunction (impotence). See " What is the most important information I should know about Sildenafil tablets? "are allergic to sildenafil or any other ingredient in sildenafil tablets. See " What are the ingredients in sildenafil tablets? "at the end of this leaflet.What should I tell my doctor before taking sildenafil tablets?Tell your doctor about all of your medical conditions, including if youhave heart problems such as angina (chest pain), heart failure, irregular heartbeats, or have had a heart attackhave a disease called pulmonary veno-occlusive disease (PVOD)have high or low blood pressure or blood circulation problemshave an eye problem called retinitis pigmentosahave or had loss of sight in one or both eyeshave any problem with the shape of your penis or Peyronie's diseasehave any blood cell problems such sickle cell anemiahave a stomach ulcer or any bleeding problemsare pregnant or planning to become pregnant. Sildenafil passes into your breast milk or if it could harm your baby.Tell your doctor about all of the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal products.Sildenafil tablets and certain other medicines can cause side effects if you take them together. "Ritonavir (Norvir ®) or other medicines used to treat HIV infectionKetoconazole (Nizoral ®)Itraconazole (Sporanox)High blood pressure medicineKnow the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.How should I take sildenafil tablets?Take sildenafil tablets exactly as your doctor tells you.Sildenafil tablets may be prescribed to you asSildenafil tabletsTake sildenafil tablets 3 times a day about 4 to 6 hours apart.Take sildenafil tablets at the same times every day.If you miss a dose, take it as soon as you remember. Talk to your doctor first.If you take too much sildenafil tablets, call your doctor or go to the nearest hospital emergency room.What are the possible side effects of sildenafil tablets?low blood pressure.Low blood pressure may cause you to feel faint or dizzy. Lie down if you feel faint or dizzy.more shortness of breath than usual.Tell your doctor if you get more short of breath after you start sildenafil tablets. More shortness of breath than usual may be due to your underlying medical condition.decreased eyesight or loss of sight in one or both eyes (NAION).If you notice a sudden decrease or loss of eyesight, talk to your doctor right away.sudden decrease or loss of hearing.If you notice a sudden decrease or loss of hearing, talk to your doctor right away.

52% of men experience some kind of erectile dysfunction throughout their life

More than twice as many sildenafil tablets-treated patients (36%) as the placebo-treated patients (14%) showed an improvement in at least one functional New York Heart Association (NYHA) class for PAH. Study 3 (Sildenafil tablets monotherapy (1 mg, 5 mg, and 20 mg three times a day)) A randomized, double-blind, parallel dose study (Study 3) was planned in 219 patients with PAH. Patients were randomized to 1 of 3 doses of Sildenafil tablets: 1 mg, 5 mg, and 20 mg, three times a day. At baseline patients had PPH (74%) or secondary PAH (26%); WHO functional class II (57%), III (41%), or IV (2%); the mean age was 44 years; and 67% were female. The majority of subjects were Asian (67%), and 28% were Caucasian.

Most Asked Questions

These increases were significantly better than those observed in the 1 mg dose group (Figure 12). Mean Change from Baseline in Six Minute Walk (meters) by Visit to Week 12 - ITT Population Sildenafil Protocol A1481244 Study 4 (Sildenafil Tablets 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 three months. HOW SUPPLIED/STORAGE AND HANDLING Sildenafil Tablets, USP 20 mg are supplied as white round, biconvex film coated tablets debossed with "R" on one side and "20" on the other side, containing sildenafil citrate equivalent to the nominally indicated amount of sildenafil as follows:Recommended Storage for Sildenafil Tablets, USP: Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature]. Sildenafil Tablets, USP 20 mg are supplied as white round, biconvex film coated tablets debossed with "R" on one side and "20" on the other side, containing sildenafil citrate equivalent to the nominally indicated amount of sildenafil as follows: Recommended Storage for Sildenafil Tablets, USP: Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature]. PATIENT COUNSELING INFORMATION See 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 tablets is also marketed as VIAGRA for erectile dysfunction. It is not possible to determine whether these events are related directly to this class of oral medicines, including sildenafil tablets, or to other diseases or medicines, to other factors, or to a combination of factors.heart attack, stroke, irregular heartbeats, and death.Most of these happened in men who already had heart problems.erections that last several hours.If you have an erection that lasts more than 4 hours, get medical help right away. If it is not treated right away, priapism can permanently damage your penis.The most common side effects with sildenafil tablets include:Nosebleed, headache, upset stomach, getting red or hot in the face (flushing), trouble sleeping, as well as fever, erection increased respiratory infection, nausea, vomiting, bronchitis, pharyngitis, runny nose, and pneumonia in children.Tell your doctor if you have any side effect that bothers you or doesn't go away.These are not all the possible side effects of sildenafil tablets.

What to do if viagra or sildenafil doesn’t work for you?

It is not possible to determine whether these events are related directly to this class of oral medicines, including sildenafil tablets, or to other diseases or medicines, to other factors, or to a combination of factors.heart attack, stroke, irregular heartbeats, and death.Most of these happened in men who already had heart problems.erections that last several hours.If you have an erection that lasts more than 4 hours, get medical help right away. If it is not treated right away, priapism can permanently damage your penis.The most common side effects with sildenafil tablets include:Nosebleed, headache, upset stomach, getting red or hot in the face (flushing), trouble sleeping, as well as fever, erection increased respiratory infection, nausea, vomiting, bronchitis, pharyngitis, runny nose, and pneumonia in children.Tell your doctor if you have any side effect that bothers you or doesn't go away.These are not all the possible side effects of sildenafil tablets.