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Liver function: If you have poor liver function you may need lower doses of this medication.

Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects.

If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Nitrate-containing medications: Sildenafil should never be taken with any medications that contain nitrates.

Blood pressure may suddenly drop to life-threatening levels if sildenafil is taken with any nitrate-containing medication (e.g., nitroglycerin tablets, spray, or patches) or any other nitrates (e.g., isosorbide dinitrate or amyl nitrite "poppers"). Dizziness, fainting spells, heart attack, or stroke may be experienced.

If use of a nitrate-containing medication is considered medically necessary, you must wait 48 hours after the last dose of sildenafil before taking a nitrate, and only under close medical supervision.

Penis deformation: As with other medications for erectile dysfunction, men with an anatomical deformation of the penis such as angulation, cavernosal fibrosis, or Peyronie's disease should be closely monitored by their doctors if they take this medication.

Prolonged erection: If an erection lasts longer than 4 hours (a rare occurrence), seek immediate medical assistance. If this condition is not treated quickly, tissue damage and permanent loss of the ability to have an erection could result. Prostate problems: Tell your doctor if you are taking medications, such as alpha-blockers (e.g., doxazosin), to treat prostate problems, as the combination of these medications with sildenafil may add to the blood pressure-lowering effect of these medications. Sexually transmitted infections: Sildenafil

does

Vision problems/eye conditions: If you experience a sudden loss of vision in one or both eyes or other vision related problems, contact your doctor immediately.

While in some cases the condition may improve over time, it can also be permanent.

This rare condition is more likely to occur if you have heart disease, high blood pressure, high cholesterol, diabetes, or eye problems, are more than 50 years old, or if you smoke.

If you have any eye conditions, such as retinitis pigmentosa or non-arteritic anterior ischemic optic neuropathy (NAION), tell your doctor.

Pregnancy and breast-feeding: Sildenafil is not intended for use by women.

Children: Sildenafil is not intended for use by children or adolescents under 18 years of age. Seniors: If you are 65 years of age or older, you may need a lower dose of this medication. What other drugs could interact with this medication?

There may be an interaction between sildenafil and any of the following: Grapefruit juice may increase the amounts of sildenafil in the blood. A high-fat meal may reduce the effectiveness of sildenafil. If you are taking any of these medications, speak with your doctor or pharmacist.

Depending on your specific circumstances, your doctor may want you to: stop taking one of the medications, change one of the medications to another, change how you are taking one or both of the medications, or leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than the ones listed above may interact with this medication.

Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications that you are taking. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

Report Side Effect Related Medicines Same active ingredients Same company Bookmark Email. Clinical particulars 4.1 Therapeutic indications 4.2 Posology and method of administration 4.3 Contraindications 4.4 Special warnings and precautions for use 4.5 Interaction with other medicinal products and other forms of interaction 4.6 Fertility, pregnancy and lactation 4.7 Effects on ability to drive and use machines 4.8 Undesirable effects 4.9 Overdose 5.

Pharmacological properties 5.1 Pharmacodynamic properties 5.2 Pharmacokinetic properties 5.3 Preclinical safety data 6.

Pharmaceutical particulars 6.1 List of excipients 6.2 Incompatibilities 6.3 Shelf life 6.4 Special precautions for storage 6.5 Nature and contents of container 6.6 Special precautions for disposal and other handling 7. Date of first authorisation/renewal of the authorisation 10. This information is intended for use by health professionals.

Each tablet contains 25 mg, 50 mg or 100 mg of sildenafil (as citrate) Excipient with known effect : Lactose monohydrate.

25 mg: White to off-white, rounded diamond-shaped tablets, of dimensions 9.2 x 6.7 mm, marked ?25? on one side. 50 mg: White to off-white, rounded diamond-shaped tablets, of dimensions 11.2 x 8.1 mm, marked ?50? on one side. 100 mg: White to off-white, rounded diamond-shaped tablets, of dimensions 14.1 x 10.2 mm, marked ?100? on one side.

Treatment of men with erectile dysfunction, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. In order for Sildenafil to be effective, sexual stimulation is required.

The recommended dose is 50 mg taken as needed approximately one hour before sexual activity.

Based on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg.

The maximum recommended dosing frequency is once per day. If Sildenafil is taken with food, the onset of activity may be delayed compared to the fasted state (see section 5.2). Dosage adjustments are not required in elderly patients (? 65 years old).

The dosing recommendations described in 'Use in adults' apply to patients with mild to moderate renal impairment (creatinine clearance = 30 - 80 mL/min).

Since sildenafil clearance is reduced in patients with severe renal impairment (creatinine clearance 150 ?M).

Given sildenafil peak plasma concentrations of approximately 1 ?M after recommended doses, it is unlikely that Sildenafil will

alter

In vivo studies: Consistent with its known effects on the nitric oxide/cGMP pathway (see section 5.1), sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors or nitrates in any form is therefore contraindicated (see section 4.3). Riociguat: Preclinical studies showed additive systemic blood pressure lowering effect when PDE5 inhibitors were combined with riociguat.

In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5 inhibitors. There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with PDE5 inhibitors, including sildenafil, is contraindicated (see section 4.3). Concomitant administration of sildenafil to patients taking alpha-blocker therapy may lead to symptomatic hypotension in a few susceptible individuals.

This is most likely to occur within 4 hours post sildenafil dosing (see sections 4.2 and 4.4). In three specific drug-drug interaction studies, the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, or 100 mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy.

In these study populations, mean additional reductions of supine blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, and mean additional reductions of standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were observed.

When sildenafil and doxazosin were administered simultaneously to patients stabilized on doxazosin therapy, there were infrequent reports of patients who experienced symptomatic postural hypotension.

These reports included dizziness and light-headedness, but not syncope. No significant interactions were shown when sildenafil (50 mg) was co-administered with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9.

Sildenafil (50 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid (150 mg). Sildenafil (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean maximum blood alcohol levels of 80 mg/dl. Pooling of the following classes of antihypertensive medication: diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive medicinal products (vasodilator and centrally-acting), adrenergic neurone blockers, calcium channel blockers and alpha-adrenoceptor blockers, showed no difference in the side effect profile in patients taking sildenafil compared to placebo treatment. In a specific interaction study, where sildenafil (100 mg) was co-administered with amlodipine in hypertensive patients, there was an additional reduction on supine systolic blood pressure of 8 mmHg. The corresponding additional reduction in supine diastolic blood pressure was 7 mmHg. These additional blood pressure reductions were of a similar magnitude to those seen when sildenafil was administered alone to healthy volunteers (see section 5.1).

Sildenafil (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.

In healthy male volunteers, sildenafil at steady state (80 mg t.i.d.) resulted in a 49.8% increase in bosentan AUC and a 42% increase in bosentan C max (125 mg b.i.d.). There are no adequate and well-controlled studies in pregnant or breast-feeding women. No relevant adverse effects were found in reproduction studies in rats and rabbits following oral administration of sildenafil. There was no effect on sperm motility or morphology after single 100 mg oral doses of sildenafil in healthy volunteers (see section 5.1).

Sildenafil Pfizer may have a minor influence on the ability to drive and use machines. As dizziness and altered vision were reported in clinical trials with sildenafil, patients should be aware of how they react to Sildenafil, before driving or operating machinery. The safety profile of Sildenafil Pfizer is based on 9,570 patients in 74 double-blind placebo-controlled clinical studies. The most commonly reported adverse reactions in clinical studies among sildenafil treated patients were headache, flushing, dyspepsia, nasal congestion, dizziness, nausea, hot flush, visual disturbance, cyanopsia and vision blurred. Adverse reactions from post-marketing surveillance has been gathered covering an estimated period >10 years.

Because not all adverse reactions are reported to the Marketing Authorisation Holder and included in the safety database, the frequencies of these reactions cannot be reliably determined.

In the table below all medically important adverse reactions, which occurred in clinical trials at an incidence greater than placebo are listed by system organ class and frequency (very common (?1/10), common (?1/100 to * Visual colour distortions**, Visual disturbance, Vision blurred.

Non-arteritic anterior ischaemic optic neuropathy (NAION), *

Retinal

Sudden cardiac death, * Respiratory, thoracic and mediastinal disorders.

Gastro oesophagael reflux disease, Abdominal pain upper, Skin and subcutaneous tissue disorders. Stevens-Johnson Syndrome (SJS), * Toxic Epidermal Necrolysis (TEN) * Musculoskeletal and connective tissue disorders.

General disorders and administration site conditions.

* Reported during post-marketing surveillance only.

**Visual colour distortions: Chloropsia, Chromatopsia, Cyanopsia, Erythropsia and Xanthopsia.

***Lacrimation disorders: Dry eye, Lacrimal disorder and Lacrimation increased.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased.

Doses of 200 mg did not result in increased efficacy but the incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision) was increased.

In cases of overdose, standard supportive measures should be adopted as required.

Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine. Pharmacotherapeutic group: Urologicals; Drugs used in erectile dysfunction. Sildenafil is an oral therapy for erectile dysfunction. with sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis. The physiological mechanism responsible for erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP.

Sildenafil has a peripheral site of action on erections.

Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects.

Studies in vitro have shown that sildenafil is selective for PDE5, which is involved in the erection process.

Its effect is more potent on PDE5 than on other known phosphodiesterases.

There is a 10-fold selectivity over PDE6 which is involved in the phototransduction pathway in the retina.

At maximum recommended doses, there is an 80-fold selectivity over PDE1, and over 700-fold over PDE2, 3, 4, 7, 8, 9, 10 and 11.

In particular, sildenafil has greater than 4,000-fold selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility. Two clinical studies were specifically designed to assess the time window after dosing during which sildenafil could produce an erection in response to sexual stimulation.

In a penile plethysmography (RigiScan) study of fasted patients, the median time to onset for those who obtained erections of 60% rigidity (sufficient for sexual intercourse) was 25 minutes (range 12-37 minutes) on sildenafil. In a separate RigiScan study, sildenafil was still able to produce an erection in response to sexual stimulation 4-5 hours post-dose. Sildenafil causes mild and transient decreases in blood pressure which, in the majority of cases, do not translate into clinical effects. The mean maximum decreases in supine systolic blood pressure following 100 mg oral dosing of sildenafil was 8.4 mmHg.

The corresponding change in supine diastolic blood pressure was 5.5 mmHg. These decreases in blood pressure are consistent with the vasodilatory effects of sildenafil, probably due to increased cGMP levels in vascular smooth muscle.

Single oral doses of sildenafil up to 100 mg in healthy volunteers produced no clinically relevant effects on ECG. In a study of the hemodynamic effects of a single oral 100 mg dose of sildenafil in 14 patients with severe coronary artery disease (CAD) (>70% stenosis of at least one coronary artery), the mean resting systolic and diastolic blood pressures decreased by 7% and 6% respectively compared to baseline.

Mean pulmonary systolic blood pressure decreased by 9%.

Sildenafil showed no effect on cardiac output, and did not impair blood flow through the stenosed coronary arteries. A double-blind, placebo-controlled exercise stress trial evaluated 144 patients with erectile dysfunction and chronic stable angina who regularly received anti-anginal medicinal products (except nitrates).

The results demonstrated no clinically relevant differences between sildenafil and placebo in time to limiting angina.

Mild and transient differences in colour discrimination (blue/green) were detected in some subjects using the Farnsworth-Munsell 100 hue test at 1 hour following a 100 mg dose, with no effects evident after 2 hours post-dose. The postulated mechanism for this change in colour discrimination is related to inhibition of PDE6, which is involved in the phototransduction cascade of the retina. Sildenafil has no effect on visual acuity or contrast sensitivity.

In a small size placebo-controlled study of patients with documented early age-related macular degeneration (n=9), sildenafil (single

dose

There was no effect on sperm motility or morphology after single 100 mg oral doses of sildenafil in healthy volunteers (see section 4.6).

In clinical trials sildenafil was administered to more than 8000 patients aged 19-87.

The following patient groups were represented: elderly (19.9%), patients with hypertension (30.9%), diabetes mellitus (20.3%), ischaemic heart disease (5.8%), hyperlipidaemia (19.8%), spinal cord injury (0.6%), depression (5.2%), transurethral resection of the prostate (3.7%), radical prostatectomy (3.3%). The following groups were not well represented or excluded from clinical trials: patients with pelvic surgery, patients post-radiotherapy, patients with severe renal or hepatic impairment and patients with certain cardiovascular conditions (see section 4.3). In fixed dose studies, the proportions of patients reporting that treatment improved their erections were 62% (25 mg), 74% (50 mg) and 82% (100 mg) compared to 25% on placebo.

In controlled clinical trials, the discontinuation rate due to sildenafil was low and similar to placebo.

Across all trials, the proportion of patients reporting improvement on sildenafil were as follows: psychogenic erectile dysfunction (84%), mixed erectile dysfunction (77%), organic erectile dysfunction (68%), elderly (67%), diabetes mellitus (59%), ischaemic heart disease (69%), hypertension (68%), TURP (61%), radical prostatectomy (43%), spinal cord injury (83%), depression (75%). The safety and efficacy of sildenafil was maintained in long-term studies.

Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is 41% (range 25-63%).

After oral dosing of sildenafil AUC and C max increase in proportion with dose over the recommended dose range (25-100 mg). When sildenafil is taken with food, the rate of absorption is reduced with a mean delay in t max of 60 minutes and a mean reduction in C max of 29%.

The mean steady state volume of distribution (V d ) for sildenafil is 105 l, indicating distribution into the tissues. After a single oral dose of 100 mg, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/mL (CV 40%). Since sildenafil (and its major circulating N-desmethyl metabolite) is 96% bound to plasma proteins, this results in the mean maximum free plasma concentration for sildenafil of 18 ng/mL (38 nM).

Protein binding is independent of total drug concentrations.

In healthy volunteers receiving sildenafil (100 mg single dose), less than 0.0002% (average 188 ng) of the administered dose was present in ejaculate 90 minutes after dosing.

Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes.

The major circulating metabolite results from N-demethylation of sildenafil.

This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% that of the parent drug.

Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised, with a terminal half-life of approximately 4 h.

The total body clearance of sildenafil is 41 l/h with a resultant terminal phase half-life of 3-5 h.

After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered oral dose). Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 90% higher plasma concentrations of sildenafil and the active N-desmethyl metabolite compared to those seen in healthy younger volunteers (18-45 years).

Due to age-differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40%.

In volunteers with mild to moderate renal impairment (creatinine clearance = 30-80 mL/min), the pharmacokinetics of sildenafil were not altered after receiving a 50 mg single oral dose. The mean AUC and C max of the N-desmethyl metabolite increased up to 126% and up to 73% respectively, compared to age-matched volunteers with no renal impairment.

However, due to high inter-subject variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance.

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