5 WARNINGS AND PRECAUTIONS

Respiratory:asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased. Skin and Appendages:urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis. Analysis of the safety database from sildenafil controlled clinical trials showed no apparent difference in adverse reactions in patients taking sildenafil with and without antihypertensive medication. This analysis was performed retrospectively and was not powered to detect any pre-specified difference in adverse reactions. The following adverse reactions have been identified during post approval use of sildenafil. Cardiovascular andCerebrovascular: serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of sildenafil.

How to use Eroxon Gel

Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy young volunteers (18-45 years) [see Clinical Pharmacology (12.3)] .Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively [see Clinical Pharmacology (12.3)]. Of the total number of subjects in clinical studies of sildenafil, 18% were 65 years and older, while 2% were 75 years and older. No overall differences in safety or efficacy were observed between older (≥ 65 years of age) and younger adult (< 65 years of age) subjects. Of the total number of subjects in the clinical study of SILDENAFIL ORAL FILM, 31% were 65 years and older. A starting dose of SILDENAFIL ORAL FILM 25 mg is recommended in patients 65 years of age and older due to the higher systemic exposure in older subjects, and larger decreases in blood pressure observed in older subjects in a clinical pharmacology study [see Dosage and Administration(2.3),Warnings and Precautions (5.1), Clinical Pharmacology(12.2].

Sildenafil may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

No dose adjustment is required for mild (CLcr=50-80 mL/min) and moderate (CLcr=30-49 mL/min) renal impairment. A starting dose of 25 mg should be considered in patients with severe renal impairment [see Dosage and Administration (2.3),Clinical Pharmacology (12.3)] . A starting dose of 25 mg should be considered in patients with any degree of hepatic impairment [see Dosage and Administration (2.3),Clinical Pharmacology (12.3)]. In studies in healthy volunteers administered single sildenafil doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but incidence rates and severities were increased. SILDENAFIL ORAL FILM (sildenafil) oral film is for treatment of erectile dysfunction and contains sildenafil citrate, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).

Interactions that increase your risk for side effects

SILDENAFIL ORAL FILM is formulated as an opaque light blue, thin, flexible oral film with the characteristic lemon and grapefruit scent. The product is available in four different strengths 25, 50, 75, or 100 mg of sildenafil equivalent to 35, 70, 105, 140 mg sildenafil citrate respectively for oral administration. SILDENAFIL ORAL sildenafil 25mg tablets FILM contains no ingredient made from a gluten-containing grain (wheat, barley, or rye). Effects ofSildenafil on Erectile Response:In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan®), after sildenafil administration compared with placebo. Most studies assessed the efficacy of sildenafil approximately 60 minutes post dose. Others were reported to have occurred hours to days after the use of sildenafil and sexual activity. It is not possible to determine whether these events are related directly to sildenafil, to sexual activity, to the patient’s underlying cardiovascular disease, to a combination of these factors, or to other factors [see Warnings and Precautions (5.1) and Patient Counseling Information (17)]. Hemic and Lymphatic: vaso-occlusive crisis: In a small, prematurely terminated study of sildenafil in patients with pulmonary arterial hypertension (PAH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported in patients who received sildenafil than in those randomized to placebo. The clinical relevance of this finding to men treated with sildenafil for ED is not known. Nervous:seizure, seizure recurrence, anxiety, and transient global amnesia. Hearing:Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including sildenafil.

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 [see Warnings and Precautions (5.4),Patient Counseling Information (17)]. Ocular:diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal edema, retinal vascular disease or bleeding, and vitreous traction/detachment. Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of sildenafil 100 mg tab phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking [see Warnings and Precautions (5.3), Patient Counseling Information (17)]. Urogenital: prolonged erection, priapism [see Warnings and Precautions (5.2) and Patient Counseling Information (17)],and hematuria. Administration of sildenafil with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil was shown to potentiate the hypotensive effects of nitrates [seeDosage and Administration (2.2), Contraindications (4.1), Clinical Pharmacology (12.2)] . Use caution when co-administering alpha-blockers with sildenafil because of potential additive blood pressure lowering effects. When sildenafil is co-administered with an alpha-blocker, patients should be stable on alpha blocker therapy prior to initiating sildenafil treatment and sildenafil should be initiated at the lowest dose [see Dosage andAdministration(2.2),Warnings and Precautions (5.5), Clinical Pharmacology (12.2)].

When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic [seeWarnings and Precautions (5.5), Clinical Pharmacology (12.2)]. It is therefore recommended not to exceed a maximum single dose of 25 mg of sildenafil in a 48 hour period [seeDosage and Administration(2.2), Warnings and Precautions (5.6), Clinical Pharmacology (12.3)]. Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in 160% and 182% increases in sildenafil Cmax and AUC, respectively.

Society and culture

Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking [see Warnings and Precautions (5.3), Patient Counseling Information (17)]. Urogenital: prolonged erection, priapism [see Warnings and Precautions (5.2) and Patient Counseling Information (17)],and hematuria. Administration of sildenafil with nitric oxide donors such as organic nitrates or organic nitrites in any form is contraindicated. Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil was shown to potentiate the hypotensive effects of nitrates [seeDosage and Administration (2.2), Contraindications (4.1), Clinical Pharmacology (12.2)] . Use caution when co-administering alpha-blockers with sildenafil because of potential additive blood pressure lowering effects.

Sildenafil side effects

When sildenafil is co-administered with an alpha-blocker, patients should be stable on alpha blocker therapy prior to initiating sildenafil treatment and sildenafil should be initiated at the lowest dose [see Dosage andAdministration(2.2),Warnings and Precautions (5.5), Clinical Pharmacology (12.2)]. When sildenafil 100 mg was co-administered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7 mmHg diastolic [seeWarnings and Precautions (5.5), Clinical Pharmacology (12.2)]. It is therefore recommended not to exceed a maximum single dose of 25 mg of sildenafil in a 48 hour period [seeDosage and Administration(2.2), Warnings and Precautions (5.6), Clinical Pharmacology (12.3)]. Co-administration of erythromycin, a moderate CYP3A4 inhibitor, resulted in 160% and 182% increases in sildenafil Cmax and AUC, respectively. A starting dose of 25 mg of sildenafil should be considered in patients taking erythromycin or strong CYP3A4 inhibitors (such as saquinavir, ketoconazole, itraconazole) [see Dosage and Administration(2.2), Clinical Pharmacology (12.3)].

Allergy warning

In a drug-drug interaction study of sildenafil 50 mg given with alcohol 0.5 g/kg, in which mean maximum blood alcohol levels of 0.08% was achieved, sildenafil did not potentiate the hypotensive effect of alcohol in healthy volunteers [see Clinical Pharmacology (12.2)] . SILDENAFIL ORAL FILM is not indicated for use in females. There are no data with the use of sildenafil for women SILDENAFIL ORAL FILM in pregnant women to inform any drug-associated risks for adverse developmental outcomes. Animal reproduction studies conducted with sildenafil did not show adverse developmental outcomes when administered during organogenesis in rats and rabbits at oral doses up to 16 and 32 times, respectively, the maximum recommended human dose (MRHD) of 100 mg/day on a mg/m2 basis ( see Data). SILDENAFIL ORAL FILM is not indicated for use in pediatric patients. A starting dose of 25 mg of sildenafil should be considered in patients taking erythromycin or strong CYP3A4 inhibitors (such as saquinavir, ketoconazole, itraconazole) [see Dosage and Administration(2.2), Clinical Pharmacology (12.3)]. In a drug-drug interaction study of sildenafil 50 mg given with alcohol 0.5 g/kg, in which mean maximum blood alcohol levels of 0.08% was achieved, sildenafil did not potentiate the hypotensive effect of alcohol in healthy volunteers [see Clinical Pharmacology (12.2)] . SILDENAFIL ORAL FILM is not indicated for use in females.

There are no data with the use of sildenafil for women SILDENAFIL ORAL FILM in pregnant women to inform any drug-associated risks for adverse developmental outcomes. Animal reproduction studies conducted with sildenafil did not show adverse developmental outcomes when administered during organogenesis in rats and rabbits at oral doses up to 16 and 32 times, respectively, the maximum recommended human dose (MRHD) of 100 mg/day on a mg/m2 basis ( see Data). SILDENAFIL ORAL FILM is not indicated for use in pediatric patients.

• Store sildenafil film tablets in a cool, dry place away from children.
• Expiry date is stamped on the package; do not use expired medication.
• Proper storage helps maintain drug efficacy and safety.

Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil resulting in approximately 84% and 107% higher plasma AUC values of sildenafil and its active N-desmethyl metabolite, respectively, compared to those seen in healthy young volunteers (18-45 years) [see Clinical Pharmacology (12.3)] .Due to age-differences in plasma protein binding, the corresponding increase in the AUC of free (unbound) sildenafil and its active N-desmethyl metabolite were 45% and 57%, respectively [see Clinical Pharmacology (12.3)]. Of the total number of subjects in clinical studies of sildenafil, 18% were 65 years and older, while 2% were 75 years and older.

What are Floradix Tablets?

No overall differences in safety or efficacy were observed between older (≥ 65 years of age) and younger adult (< 65 years of age) subjects.

Of the total number of subjects in the clinical study of SILDENAFIL ORAL FILM, 31% were 65 years and older. A starting dose of SILDENAFIL ORAL FILM 25 mg is recommended in patients 65 years of age and older due to the higher systemic exposure in older subjects, and larger decreases in blood pressure observed in older subjects in a clinical pharmacology study [see Dosage and Administration(2.3),Warnings and Precautions (5.1), Clinical Pharmacology(12.2]. No dose adjustment is required for mild (CLcr=50-80 mL/min) and moderate (CLcr=30-49 mL/min) renal impairment. A starting dose of 25 mg should be considered in patients with severe renal impairment [see Dosage and Administration (2.3),Clinical Pharmacology (12.3)] .

Avarante 10mg - 2 Tablets

A starting dose of 25 mg should be considered in patients with any degree of hepatic impairment [see Dosage and Administration (2.3),Clinical Pharmacology (12.3)]. In studies in healthy volunteers administered single sildenafil doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but incidence rates and severities were increased. SILDENAFIL ORAL FILM (sildenafil) oral film is for treatment of erectile dysfunction and contains sildenafil citrate, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).

Key features of Sildenafil 50mg Tablets

Effects ofSILDENAFIL ORAL FILM on Blood Pressure: Single oral doses (50 mg, 75 mg, 100 mg) of VYBRIQYE administered to 12 healthy young volunteers produced decreases in supine blood pressure. The placebo-subtracted mean maximum decreases in systolic/diastolic blood pressure were 6.1/2.8 mmHg after a single 100 mg dose. Subjects were under fasting conditions and lay in the supine position for the first 4 hours post-dose and were not initially titrated. The decrease in supine blood pressure was most notable approximately 1-2 hours after dosing. Figure1: Mean Change from Baseline inSupineSystolic Blood Pressure, Healthy Volunteers Single oral doses of 50 mg, 75 mg, 100 mg of SILDENAFIL ORAL FILM administered to 12 elderly volunteers produced decreases in supine blood pressure.

8.2 Lactation

The placebo-subtracted maximum mean decreases in systolic/diastolic blood pressure were 13.7/8.5 mmHg after a single 100 mg dose. The decrease in supine blood pressure was generally observed from 15 min to 4 h post-dose. Figure2: Mean Change from Baseline inSupineSystolic Blood Pressure,Elderly Effects ofSildenafil on Blood Pressure When Nitroglycerin is Subsequently Administered:Based on the pharmacokinetic profile of a single 100 mg sildenafil oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL).

7.1 Nitrates

SILDENAFIL ORAL FILM is formulated as an opaque light blue, thin, flexible oral film with the characteristic lemon and grapefruit scent. The product is available in four different strengths 25, 50, 75, or 100 mg of sildenafil equivalent to 35, 70, 105, 140 mg sildenafil citrate respectively for oral administration.

4. Contraindications

SILDENAFIL ORAL sildenafil 25mg tablets FILM contains no ingredient made from a gluten-containing grain (wheat, barley, or rye).

• Sildenafil film tablets typically start working within 30-60 minutes.
• The recommended dose varies, often 50mg before sexual activity.
• Do not take more than one tablet per 24 hours.

Effects ofSildenafil on Erectile Response:In eight double-blind, placebo-controlled crossover studies of patients with either organic or psychogenic erectile dysfunction, sexual stimulation resulted in improved erections, as assessed by an objective measurement of hardness and duration of erections (RigiScan®), after sildenafil administration compared with placebo. Most studies assessed the efficacy of sildenafil approximately 60 minutes post dose. Effects ofSILDENAFIL ORAL FILM on Blood Pressure: Single oral doses (50 mg, 75 mg, 100 mg) of VYBRIQYE administered to 12 healthy young volunteers produced decreases in supine blood pressure. The placebo-subtracted mean maximum decreases in systolic/diastolic blood pressure were 6.1/2.8 mmHg after a single 100 mg dose.

Supplemental data

Respiratory:asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, sputum increased, cough increased. Skin and Appendages:urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis. Analysis of the safety database from sildenafil controlled clinical trials showed no apparent difference in adverse reactions in patients taking sildenafil with and without antihypertensive medication. This analysis was performed retrospectively and was not powered to detect any pre-specified difference in adverse reactions. The following adverse reactions have been identified during post approval use of sildenafil.

What are the most common side effects of sildenafil?

Cardiovascular andCerebrovascular: serious cardiovascular, cerebrovascular, and vascular events, including myocardial infarction, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension, subarachnoid and intracerebral hemorrhages, and pulmonary hemorrhage have been reported post-marketing in temporal association with the use of sildenafil. Others were reported to have occurred hours to days after the use of sildenafil and sexual activity. It is not possible to determine whether these events are related directly to sildenafil, to sexual activity, to the patient’s underlying cardiovascular disease, to a combination of these factors, or to other factors [see Warnings and Precautions (5.1) and Patient Counseling Information (17)]. Hemic and Lymphatic: vaso-occlusive crisis: In a small, prematurely terminated study of sildenafil in patients with pulmonary arterial hypertension (PAH) secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were more commonly reported in patients who received sildenafil than in those randomized to placebo. The clinical relevance of this finding to men treated with sildenafil for ED is not known.

Missed Dose

Nervous:seizure, seizure recurrence, anxiety, and transient global amnesia. Hearing:Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including sildenafil. 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 [see Warnings and Precautions (5.4),Patient Counseling Information (17)]. Ocular:diplopia, temporary vision loss/decreased vision, ocular redness or bloodshot appearance, ocular burning, ocular swelling/pressure, increased intraocular pressure, retinal edema, retinal vascular disease or bleeding, and vitreous traction/detachment. Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely post-marketing in temporal association with the use of sildenafil 100 mg tab phosphodiesterase type 5 (PDE5) inhibitors, including sildenafil. Subjects were under fasting conditions and lay in the supine position for the first 4 hours post-dose and were not initially titrated. The decrease in supine blood pressure was most notable approximately 1-2 hours after dosing. Figure1: Mean Change from Baseline inSupineSystolic Blood Pressure, Healthy Volunteers Single oral doses of 50 mg, 75 mg, 100 mg of SILDENAFIL ORAL FILM administered to 12 elderly volunteers produced decreases in supine blood pressure. The placebo-subtracted maximum mean decreases in systolic/diastolic blood pressure were 13.7/8.5 mmHg after a single 100 mg dose. The decrease in supine blood pressure was generally observed from 15 min to 4 h post-dose.

• Possible interactions include medications for HIV, antibiotics, and blood pressure.
• Overdose symptoms include severe headaches and chest pain.
• Seek immediate medical attention if adverse reactions occur.

Figure2: Mean Change from Baseline inSupineSystolic Blood Pressure,Elderly Effects ofSildenafil on Blood Pressure When Nitroglycerin is Subsequently Administered:Based on the pharmacokinetic profile of a single 100 mg sildenafil oral dose given to healthy normal volunteers, the plasma levels of sildenafil at 24 hours post dose are approximately 2 ng/mL (compared to peak plasma levels of approximately 440 ng/mL).