6 ADVERSE REACTIONS

5.6 Adverse Reactions with the Concomitant Use of Ritonavir
5.5 Visual Loss
AN 355
What does Sildenafil Citrate look like?

Ingredient	Quantity per Tablet	Function	Notes
Sildenafil Citrate	50 mg	Active ingredient	Main component
Microcrystalline Cellulose	20 mg	Filler and binder	Increases tablet stability
Magnesium Stearate	2 mg	Lubricant	Ensures smooth manufacturing
Starch	10 mg	Diluent	Helps with disintegration

Adverse reactions were generally transient and mild to moderate in nature.Table 1. Most Common Adverse Reactions in Patients with PAH in Study 1 (More Frequent in Sildenafil-Treated Patients than Placebo-Treated Patients and Incidence ≥3% in Sildenafil-Treated Patients)At doses higher than the recommended 20 mg three times a day, there was a greater incidence of some adverse reactions including flushing, diarrhea, myalgia and visual disturbances. Visual disturbances were identified as mild and transient, and were predominately color-tinge to vision, but also increased sensitivity to light or blurred vision.The incidence of retinal hemorrhage with sildenafil 20 mg three times a day was 1.4% versus 0% placebo and for all sildenafil doses studied was 1.9% versus 0% placebo.

5.6 Adverse Reactions with the Concomitant Use of Ritonavir

No patients died during the 16-week controlled study.After completing the 16-week controlled study, a patient originally randomized to sildenafil remained on his/her dose of sildenafil or, if originally randomized to placebo, was randomized to low-, medium-, or high-dose sildenafil. After all patients completed 16 weeks of follow-up in the controlled study, the blind was broken and doses were adjusted as clinically indicated. Patients treated with sildenafil were followed for a median of 4.6 years (range 2 days to 8.6 years). Mortality during the long-term study, by originally assigned dose, is shown in Figure 6:Figure 6: Kaplan-Meier Plot of Mortality by Sildenafil Dose.During the study, there were 42 reported deaths, with 37 of these deaths reported prior to a decision to titrate subjects to a lower dosage because of a finding of increased mortality with increasing sildenafil doses. For the survival analysis which included 37 deaths, the hazard ratio for high dose compared to low dose was 3.9, p=0.007.

Regional issues

Causes of death were typical of patients with PAH. Use of sildenafil, particularly chronic use, is not recommended in children.8.5 Geriatric UseClinical studies of sildenafil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Severe impairment has not been studied [see Clinical Pharmacology 12.3)].8.7 Patients with Renal ImpairmentNo dose adjustment is required (including severe impairment CLcr < 30 mL/min) [see Clinical Pharmacology (12.3)].

Altitude sickness

Sildenafil tablets are classified as phosphodiesterase inhibitors.
White sildenafil tablets are available by prescription only.
They should not be used with nitrates due to risk of dangerous drops in blood pressure.
Certain medications may interact with sildenafil, including antibiotics and antifungals.
The tablets are designed to last approximately 4-6 hours.
Overuse can lead to adverse effects like dizziness or vision changes.
Sildenafil helps men with erectile dysfunction achieve and maintain erections.
The medicine is not an aphrodisiac and requires sexual stimulation.
The tablets should be stored in a cool, dry place away from children.
Beware of counterfeit sildenafil tablets sold online.
Always verify the legitimacy of the medication before use.

Adverse Reactions (%) in patients with PAH in Study 2 (incidence in Sildenafil + Epoprostenol group at least 6% greater than Epoprostenol group)6.2 Postmarketing ExperienceThe following adverse reactions have been identified during post approval use of sildenafil (marketed for both PAH and erectile dysfunction).

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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 systemSeizure, seizure recurrenceOphthalmologicNAION [see Warnings and Precautions (5.5) and Patient Counseling Information (17)]. The following serious adverse events are discussed elsewhere in the labeling: 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. Safety data of sildenafil in adults were obtained from the 12-week, placebo-controlled clinical study (Study 1) and an open-label extension study in 277 sildenafil-treated patients with PAH, WHO Group I [see Clinical Studies (14)].

5.5 Visual Loss

The overall frequency of discontinuation in sildenafil-treated patients on 20 mg three times a day was 3% and was the same for the placebo group.

AN 355

It is not possible to determine whether these reported events are related directly to the use of sildenafil, to the patient's underlying risk factors for hearing loss, a combination of these factors, or to other factors. 6 ADVERSE REACTIONS The following serious adverse events are discussed elsewhere in the labeling:• Mortality with pediatric use[see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)]• Hypotension [see Warnings and Precautions (5.2)]• Vision loss [see Warnings and Precautions (5.5)]• Hearing loss [see Warnings and Precautions (5.6)]• Priapism [see Warnings and Precautions (5.8)]• Vaso-occlusive crisis [see Warnings and Precautions (5.9) ]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.Safety data of sildenafil in adults were obtained from the 12-week, placebo-controlled clinical study (Study 1) and an open-label extension study in 277 sildenafil-treated patients with PAH, WHO Group I [see Clinical Studies (14)].The overall frequency of discontinuation in sildenafil-treated patients on 20 mg three times a day was 3% and was the same for the placebo group.In Study 1, the adverse reactions that were reported by at least 3% of sildenafil-treated patients (20 mg three times a day) 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.Table 1. Most Common Adverse Reactions in Patients with PAH in Study 1 (More Frequent in Sildenafil-Treated Patients than Placebo-Treated Patients and Incidence ≥3% in Sildenafil-Treated Patients)At doses higher than the recommended 20 mg three times a day, there was a greater incidence of some adverse reactions including flushing, diarrhea, myalgia and visual disturbances. Visual disturbances were identified as mild and transient, and were predominately color-tinge to vision, but also increased sensitivity to light or blurred vision.The incidence of retinal hemorrhage with sildenafil 20 mg three times a day was 1.4% versus 0% placebo and for all sildenafil doses studied was 1.9% versus 0% placebo.

Before taking sildenafil,

The incidence of eye hemorrhage at both 20 mg three times a day and at all doses studied was 1.4% for sildenafil versus 1.4% for placebo. The patients experiencing these reactions had risk factors for hemorrhage including concurrent anticoagulant therapy.In a placebo-controlled fixed dose titration study (Study 2) 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, the adverse reactions that were more frequent in the sildenafil + epoprostenol group than in the epoprostenol group (greater than 6% difference) are shown in Table 2 [see Clinical Studies (14)].Table 2. Adverse Reactions (%) in patients with PAH in Study 2 (incidence in Sildenafil + Epoprostenol group at least 6% greater than Epoprostenol group)6.2 Postmarketing ExperienceThe following adverse reactions have been identified during post approval use of sildenafil (marketed for both PAH and erectile dysfunction). 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 systemSeizure, seizure recurrenceOphthalmologicNAION [see Warnings and Precautions (5.5) and Patient Counseling Information (17)]. The following serious adverse events are discussed elsewhere in the labeling: 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.

How does sildenafil work (mechanism of action)?

Safety data of sildenafil in adults were obtained from the 12-week, placebo-controlled clinical study (Study 1) and an open-label extension study in 277 sildenafil-treated patients with PAH, WHO Group I [see Clinical Studies (14)]. The overall frequency of discontinuation in sildenafil-treated patients on 20 mg three times a day was 3% and was the same for the placebo group. In Study 1, the adverse reactions that were reported by at least 3% of sildenafil-treated patients (20 mg three times a day) and were more frequent in sildenafil-treated patients than in placebo-treated patients are shown in Table 1. Most Common Adverse Reactions in Patients with PAH sildenafil uk price in Study 1 (More Frequent in Sildenafil-Treated Patients than Placebo-Treated Patients and Incidence ≥3% in Sildenafil-Treated Patients) At doses higher than the recommended 20 mg three times a day, there was a greater incidence of some adverse reactions including flushing, diarrhea, myalgia and visual disturbances. Visual disturbances were identified as mild and transient, and were predominately color-tinge to vision, but also increased sensitivity to light or blurred vision. In Study 1, the adverse reactions that were reported by at least 3% of sildenafil-treated patients (20 mg three times a day) and were more frequent in sildenafil-treated patients than in placebo-treated patients are shown in Table 1. Most Common Adverse Reactions in Patients with PAH sildenafil uk price in Study 1 (More Frequent in Sildenafil-Treated Patients than Placebo-Treated Patients and Incidence ≥3% in Sildenafil-Treated Patients) At doses higher than the recommended 20 mg three times a day, there was a greater incidence of some adverse reactions including flushing, diarrhea, myalgia and visual disturbances.

What does Sildenafil Citrate look like?

7 DRUG INTERACTIONS NitratesConcomitant use of sildenafil with nitrates in any form is contraindicated [see Contraindications (4)].Ritonavir and other Potent CYP3A InhibitorsConcomitant use of sildenafil with ritonavir and other potent CYP3A inhibitors is not recommended [see Clinical Pharmacology (12.3)].Other drugs that reduce blood pressureAlpha blockers. In drug-drug interaction studies, sildenafil (25 mg, 50 mg, or 100 mg) and the alpha-blocker doxazosin (4 mg or 8 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy. In these study populations, mean additional reductions of supine systolic and diastolic blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, respectively, were observed. Mean additional reductions of standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were also observed. There were infrequent reports of patients who experienced symptomatic postural hypotension.

What are the serious side effects of sildenafil?

These reports included dizziness and light-headedness, but not syncope.Amlodipine. When sildenafil 100 mg oral was co-administered with amlodipine, 5 mg or 10 mg oral, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic.Monitor blood pressure when co-administering blood pressure lowering drugs with sildenafil [see Warnings and Precautions (5.2)]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Clinical ConsiderationsDisease-Associated Maternal and/or Embryo/Fetal RiskPregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death.DataAnimal DataNo evidence of teratogenicity, embryotoxicity, or fetotoxicity was observed in pregnant rats or rabbits dosed with sildenafil 200 mg/kg/day during organogenesis, a level that is, on a mg/m2 basis, 32-and 65-times, respectively, the recommended human dose (RHD) of 20 mg three times a day. Limited clinical data during lactation preclude a clear determination of the risk of sildenafil to an infant during lactation.8.4 Pediatric UseIn a randomized, double-blind, multi-center, placebo-controlled, parallel-group, dose-ranging study, 234 patients with PAH, aged 1 to 17 years, body weight greater than or equal to 8 kg, were randomized, on the basis of body weight, to three dose levels of sildenafil, or placebo, for 16 weeks of treatment.

What is sildenafil used for?

Most patients had mild to 200mg sildenafil citrate moderate symptoms at baseline: WHO Functional Class I (32%), II (51%), III (15%), or IV (0.4%). One-third of patients had primary PAH; two-thirds had secondary PAH (systemic-to-pulmonary shunt in 37%; surgical repair in 30%). Sixty-two percent of patients were female. Drug or placebo was administered three times a day.The primary objective of the study was to assess the effect of sildenafil on exercise capacity as measured by cardiopulmonary exercise testing in pediatric patients developmentally able to perform the test (n = 115). Administration of sildenafil did not result in a statistically significant improvement in exercise capacity in those patients. Visual disturbances were identified as mild and transient, and were predominately color-tinge to vision, but also increased sensitivity to light or blurred vision. 7 DRUG INTERACTIONS NitratesConcomitant use of sildenafil with nitrates in any form is contraindicated [see Contraindications (4)].Ritonavir and other Potent CYP3A InhibitorsConcomitant use of sildenafil with ritonavir and other potent CYP3A inhibitors is not recommended [see Clinical Pharmacology (12.3)].Other drugs that reduce blood pressureAlpha blockers. In drug-drug interaction studies, sildenafil (25 mg, 50 mg, or 100 mg) and the alpha-blocker doxazosin (4 mg or 8 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy. In these study populations, mean additional reductions of supine systolic and diastolic blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, respectively, were observed. Mean additional reductions of standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were also observed. There were infrequent reports of patients who experienced symptomatic postural hypotension. These reports included dizziness and light-headedness, but not syncope.Amlodipine. When sildenafil 100 mg oral was co-administered with amlodipine, 5 mg or 10 mg oral, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic.Monitor blood pressure when co-administering blood pressure lowering drugs with sildenafil [see Warnings and Precautions (5.2)].

Form	Available Strengths	Description	Notes
Tablets	25 mg, 50 mg, 100 mg	Standard oral tablets	Most common dosage
Sublingual Tabs	25 mg	Dissolve under tongue	Rapid absorption
Liquid Suspension	10 mg/5 mL	For easy dosing, especially in children	Requires precise measurement

In the U.S.

Sildenafil tablets are usually small, oval-shaped, and white in color.
Their availability depends on your country’s healthcare regulations.
Sildenafil's impact varies based on diet, health, and alcohol use.
Follow all instructions regarding dose timing for optimal results.
Always store sildenafil out of direct sunlight and moisture.
Consult a healthcare professional if sildenafil fails to produce desired effects.
Do not skip doses if you miss a scheduled dose; consult your doctor.
Sildenafil is not a cure but helps manage symptoms of ED.
Be aware of the potential for a drop in blood pressure post-dose.
Use sildenafil responsibly to prevent side effects and interactions.
Always verify that the medication is prescribed specifically for you.

general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.Clinical ConsiderationsDisease-Associated Maternal and/or Embryo/Fetal RiskPregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death.DataAnimal DataNo evidence of teratogenicity, embryotoxicity, or fetotoxicity was observed in pregnant rats or rabbits dosed with sildenafil 200 mg/kg/day during organogenesis, a level that is, on a mg/m2 basis, 32-and 65-times, respectively, the recommended human dose (RHD) of 20 mg three times a day. Limited clinical data during lactation preclude a clear determination of the risk of sildenafil to an infant during lactation.8.4 Pediatric UseIn a randomized, double-blind, multi-center, placebo-controlled, parallel-group, dose-ranging study, 234 patients with PAH, aged 1 to 17 years, body weight greater than or equal to 8 kg, were randomized, on the basis of body weight, to three dose levels of sildenafil, or placebo, for 16 weeks of treatment. Most patients had mild to 200mg sildenafil citrate moderate symptoms at baseline: WHO Functional Class I (32%), II (51%), III (15%), or IV (0.4%). One-third of patients had primary PAH; two-thirds had secondary PAH (systemic-to-pulmonary shunt in 37%; surgical repair in 30%). Sixty-two percent of patients were female. Drug or placebo was administered three times a day.The primary objective of the study was to assess the effect of sildenafil on exercise capacity as measured by cardiopulmonary exercise testing in pediatric patients developmentally able to perform the test (n = 115). Administration of sildenafil did not result in a statistically significant improvement in exercise capacity in those patients. No patients died during the 16-week controlled study.After completing the 16-week controlled study, a patient originally randomized to sildenafil remained on his/her dose of sildenafil or, if originally randomized to placebo, was randomized to low-, medium-, or high-dose sildenafil. After all patients completed 16 weeks of follow-up in the controlled study, the blind was broken and doses were adjusted as clinically indicated. Patients treated with sildenafil were followed for a median of 4.6 years (range 2 days to 8.6 years). Mortality during the long-term study, by originally assigned dose, is shown in Figure 6:Figure 6: Kaplan-Meier Plot of Mortality by Sildenafil Dose.During the study, there were 42 reported deaths, with 37 of these deaths reported prior to a decision to titrate subjects to a lower dosage because of a finding of increased mortality with increasing sildenafil doses. For the survival analysis which included 37 deaths, the hazard ratio for high dose compared to low dose was 3.9, p=0.007. Causes of death were typical of patients with PAH. Use of sildenafil, particularly chronic use, is not recommended in children.8.5 Geriatric UseClinical studies of sildenafil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

White sildenafil tablets are used to treat erectile dysfunction.
They are often sold under brand names like Viagra.
The standard dose for sildenafil is 50 mg.
White sildenafil tablets contain the active ingredient sildenafil citrate.
These tablets typically come in 25 mg, 50 mg, and 100 mg doses.
They work by increasing blood flow to the penis.
Sildenafil tablets should be taken about 30-60 minutes before activity.
They are most effective when taken on an empty stomach.
Common side effects include headache, flushing, and upset stomach.
Always consult a healthcare provider before using sildenafil.
Purchasing from reputable sources ensures quality and safety.

Severe impairment has not been studied [see Clinical Pharmacology 12.3)].8.7 Patients with Renal ImpairmentNo dose adjustment is required (including severe impairment CLcr < 30 mL/min) [see Clinical Pharmacology (12.3)].