Ergos

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ERGOS® (ERGOS®)

Composition:

Active substance: sildenafil;

1 tablet contains 50 mg of sildenafil;

Excipients: lactose monohydrate, magnesium gluconate, sugar powder, calcium stearate, lemon flavor, tartrazine dye (E 102).

Pharmaceutical form. Tablets.

Main physicochemical properties: yellowish, biconvex tablets with speckles, with or without a score line on one side and the company's logo on the other.

Pharmacotherapeutic group. Agents used in erectile dysfunction. Sildenafil. ATC code G04BE03.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action. Sildenafil is an oral medication intended for the treatment of erectile dysfunction. During sexual stimulation, the drug restores impaired erectile function by enhancing blood flow to the penis.

The physiological mechanism leading to erection involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Released nitric oxide activates the enzyme guanylate cyclase, which stimulates an increase in the level of cyclic guanosine monophosphate (cGMP), resulting in relaxation of the smooth muscles of the corpus cavernosum and promoting blood inflow.

Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE-5) in the corpus cavernosum, where PDE-5 is responsible for cGMP breakdown. The effect of sildenafil on erection is peripheral. Sildenafil does not exert a direct relaxing effect on isolated human corpus cavernosum tissue, but strongly enhances the relaxing effect of NO on this tissue. During activation of the NO/cGMP metabolic pathway, which occurs during sexual stimulation, sildenafil's inhibition of PDE-5 leads to increased cGMP levels in the corpus cavernosum. Thus, for sildenafil to produce the desired pharmacological effect, sexual stimulation is required.

Effect on pharmacodynamics. In vitro studies have demonstrated that sildenafil is selective for PDE-5, which actively participates in the erectile process. The effect of sildenafil on PDE-5 is more potent than on other known phosphodiesterases. This effect is 10 times more potent than its effect on PDE-6, which is involved in phototransduction in the retina. At maximum recommended doses, sildenafil's selectivity for PDE-5 is 80 times greater than for PDE-1, 700 times higher than for PDE-2, PDE-3, PDE-4, PDE-7, PDE-8, PDE-9, PDE-10, and PDE-11. Specifically, sildenafil's selectivity for PDE-5 is 4000 times greater than for PDE-3—an isoform of cAMP-specific phosphodiesterase involved in regulating cardiac contractility.

Pharmacokinetics.

Absorption. Sildenafil is rapidly absorbed. Maximum plasma concentration (Cmax) is achieved within 30–120 minutes (median 60 minutes) after oral administration on an empty stomach. The mean absolute bioavailability after oral administration is 41% (range 25–63%). Within the recommended dose range (25–100 mg), the area under the concentration–time curve (AUC) and Cmax of sildenafil increase proportionally with dose.

When sildenafil is taken with food, the extent of absorption is reduced, with a mean delay in time to reach maximum concentration (Tmax) of 60 minutes and a mean reduction in Cmax by 29%.

Distribution. The mean steady-state volume of distribution (Vd) is 105 liters, indicating extensive distribution of the drug into body tissues. After a single 100 mg oral dose of sildenafil, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/mL (coefficient of variation 40%). Since binding of sildenafil and its major N-desmethyl metabolite to plasma proteins reaches 96%, the mean free sildenafil Cmax is 18 ng/mL (38 nmol). The degree of plasma protein binding is independent of total sildenafil concentrations.

In healthy volunteers who received a single 100 mg dose of sildenafil, less than 0.0002% (mean 188 ng) of the administered dose was detected in semen after 90 minutes.

Biotransformation. Sildenafil metabolism is primarily mediated by hepatic microsomal isoenzymes CYP3A4 (main pathway) and CYP2C9 (minor pathway). The major circulating metabolite is formed via N-demethylation of sildenafil. The metabolite's selectivity for PDE-5 is comparable to that of sildenafil, and its activity against PDE-5 is approximately 50% of the parent compound. Plasma concentration of this metabolite is about 40% of the plasma concentration of sildenafil. The N-desmethyl metabolite undergoes further metabolism, and its elimination half-life is approximately 4 hours.

Elimination. Total clearance of sildenafil is 41 L/h, resulting in an elimination half-life of 3–5 hours. After both oral and intravenous administration, excretion of sildenafil metabolites occurs primarily in feces (approximately 80% of the orally administered dose) and to a lesser extent in urine (approximately 13% of the orally administered dose).

Pharmacokinetics in special patient populations.

Elderly patients. In healthy elderly volunteers (aged 65 years and older), reduced clearance of sildenafil was observed, resulting in approximately 90% higher plasma concentrations of sildenafil and its active N-desmethyl metabolite compared to younger healthy volunteers (18–45 years). Due to age-related differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40%.

Renal impairment. In volunteers with mild to moderate renal impairment (creatinine clearance 30–80 mL/min), the pharmacokinetics of sildenafil remained unchanged after a single 50 mg oral dose. Mean AUC and Cmax of the N-desmethyl metabolite increased by up to 126% and 73%, respectively, compared to age-matched volunteers with normal renal function. However, due to high individual variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance <30 mL/min), sildenafil clearance was reduced, resulting in mean increases in AUC and Cmax by 100% and 88%, respectively, compared to age-matched volunteers with normal renal function. Additionally, AUC and Cmax of the N-desmethyl metabolite were significantly increased by 200% and 79%, respectively.

Hepatic impairment. In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh classes A and B), sildenafil clearance was reduced, leading to increases in AUC (84%) and Cmax (47%) compared to age-matched volunteers with normal liver function. The pharmacokinetics of sildenafil in patients with severe hepatic impairment have not been studied.

Clinical characteristics.

Indications.

ERGOS® is recommended for use in men with erectile dysfunction, which is defined as the inability to achieve or maintain an erection of the penis sufficient for successful sexual intercourse.

For effective action of the ERGOS® preparation, sexual stimulation is required.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
• Concomitant use with nitric oxide donors (such as amyl nitrite) or nitrates in any form, since it is known that sildenafil affects the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) metabolic pathways and potentiates the hypotensive effect of nitrates.
• Concomitant use of PDE-5 inhibitors (including sildenafil) with guanylate cyclase stimulators such as riociguat, as this may lead to symptomatic hypotension (see section "Interaction with other medicinal products and other types of interactions").
• Conditions in which sexual activity is not recommended (e.g., severe cardiovascular disorders such as unstable angina or severe heart failure).
• Unilateral vision loss due to non-arteritic anterior ischemic optic neuropathy, regardless of whether this condition is associated with prior use of PDE-5 inhibitors or not.
• Presence of conditions such as severe hepatic impairment, arterial hypotension (blood pressure below 90/50 mm Hg), recent stroke or myocardial infarction, and known hereditary degenerative retinal disorders such as retinitis pigmentosa (a small number of such patients have genetic disorders of retinal phosphodiesterases), since the safety of sildenafil has not been studied in these patient subgroups.

Interaction with other medicinal products and other types of interactions.

Effect of other medicinal products on sildenafil.

In vitro studies. Sildenafil metabolism is primarily mediated by cytochrome P450 isoenzyme 3A4 (major pathway) and isoenzyme 2C9 (minor pathway). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance, while inducers of these isoenzymes may increase sildenafil clearance.

In vivo studies. Population pharmacokinetic analysis of clinical trial data demonstrated reduced sildenafil clearance when co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although an increased frequency of adverse events was not observed when sildenafil was used concomitantly with CYP3A4 inhibitors, consideration should be given to initiating sildenafil therapy at a dose of 25 mg.

Concomitant administration of the HIV protease inhibitor ritonavir, a very potent inhibitor of P450, at steady-state concentration (500 mg once daily) and sildenafil (single 100 mg dose) resulted in a 300% increase (4-fold) in sildenafil Cmax and a 1000% increase (11-fold) in plasma AUC. After 24 hours, plasma levels of sildenafil were still approximately 200 ng/mL compared to approximately 5 ng/mL when sildenafil was administered alone, consistent with the significant effect of ritonavir on a broad range of P450 substrates. Sildenafil does not affect the pharmacokinetics of ritonavir. Due to these pharmacokinetic data, concomitant use of sildenafil and ritonavir is not recommended (see section "Special precautions for use"); in any case, the maximum dose of sildenafil should not exceed 25 mg within 48 hours.

Concomitant administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at a dose providing steady-state concentration (1200 mg three times daily) and sildenafil (single 100 mg dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC. No effect of sildenafil on the pharmacokinetics of saquinavir was observed (see section "Dosage and administration"). It is expected that more potent CYP3A4 inhibitors, such as ketoconazole and itraconazole, will have a more pronounced effect.

When sildenafil (100 mg single dose) was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg twice daily for 5 days), a 182% increase in sildenafil AUC was observed. In healthy male volunteers, azithromycin (500 mg daily for 3 days) had no effect on AUC, Cmax, Tmax, elimination rate constant, or subsequent half-life of sildenafil or its major circulating metabolite. Cimetidine (a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor) at a dose of 800 mg, when co-administered with sildenafil 50 mg in healthy volunteers, increased plasma concentration of sildenafil by 56%.

Grapefruit juice is a weak inhibitor of intestinal CYP3A4 and may cause a moderate increase in plasma levels of sildenafil.

Single-dose administration of antacids (magnesium hydroxide/aluminum hydroxide) did not affect sildenafil bioavailability.

Although specific interaction studies with all medicinal products have not been conducted (based on population pharmacokinetic analysis), the pharmacokinetics of sildenafil were not altered when co-administered with medicinal products belonging to the CYP2C9 inhibitor group (tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, loop and potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, calcium antagonists, β-adrenoreceptor antagonists, or CYP450 metabolism inducers (such as rifampicin, barbiturates).

In a study involving healthy male volunteers, concomitant administration of the endothelin antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9, and possibly CYP2C19) at steady state (125 mg twice daily) and sildenafil at steady state (80 mg three times daily) resulted in a 62.6% and 55.4% reduction in AUC and Cmax of sildenafil, respectively. Therefore, concomitant use of potent CYP3A4 inducers such as rifampicin may lead to a more pronounced decrease in plasma concentration of sildenafil.

Nicorandil is a hybrid of a potassium channel activator and a nitrate. The nitrate component implies the possibility of serious interaction with sildenafil.

Effect of sildenafil on other medicinal products.

In vitro studies. Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 (IC50 >150 µmol). Since peak plasma concentrations of sildenafil are approximately 1 µmol, the effect of the drug on the clearance of substrates of these isoenzymes is unlikely.

There are no data on the interaction between sildenafil and non-specific phosphodiesterase inhibitors such as theophylline and dipyridamole.

In vivo studies. Since it is known that sildenafil affects NO/cGMP metabolism, it has been established that sildenafil potentiates the hypotensive effect of nitrates; therefore, its concomitant use with nitric oxide donors or nitrates in any form is contraindicated (see section "Contraindications").

Riociguat. Preclinical studies demonstrated an additive systemic blood pressure-lowering effect when PDE-5 inhibitors were used concomitantly with riociguat. Clinical studies have shown that riociguat enhances the hypotensive effect of PDE-5 inhibitors. In patients participating in the study, no positive clinical effect was observed with concomitant use of PDE-5 inhibitors and riociguat. Concomitant use of riociguat with PDE-5 inhibitors, including sildenafil, is contraindicated (see section "Contraindications").

Concomitant use of sildenafil and α-adrenoreceptor blockers may lead to symptomatic hypotension in some susceptible patients. This reaction most commonly occurred within 4 hours after sildenafil administration (see sections "Special precautions for use" and "Dosage and administration"). In three specific interaction studies, doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, and 100 mg) were administered concomitantly to patients with benign prostatic hyperplasia whose condition was stabilized on doxazosin. In these populations, mean additional reductions in supine blood pressure were 7/7 mm Hg, 9/5 mm Hg, and 8/4 mm Hg, and mean reductions in standing blood pressure were 6/6 mm Hg, 11/4 mm Hg, and 4/5 mm Hg, respectively. Symptomatic orthostatic hypotension has occasionally been reported when sildenafil was used concomitantly with doxazosin in patients whose condition was stabilized on doxazosin. These reports described episodes of dizziness and presyncope, but not syncope.

No significant interactions were observed when sildenafil (50 mg) was co-administered with tolbutamide (250 mg) or warfarin (40 mg), both metabolized by CYP2C9.

Sildenafil (50 mg) did not prolong bleeding time induced by acetylsalicylic acid (150 mg).

Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers at a mean maximum blood ethanol level of 80 mg/dL.

In patients taking sildenafil, no differences in adverse effect profile were observed compared to placebo when co-administered with classes of antihypertensive drugs such as diuretics, β-adrenoreceptor blockers, angiotensin-converting enzyme inhibitors, angiotensin II antagonists, antihypertensive drugs (vasodilators and centrally acting), adrenergic neuron blockers, calcium channel blockers, and α-adrenoreceptor blockers. In a specific interaction study, concomitant administration of sildenafil (100 mg) and amlodipine in patients with arterial hypertension resulted in an additional 8 mm Hg reduction in supine systolic blood pressure. The corresponding reduction in diastolic blood pressure was 7 mm Hg. These additional blood pressure reductions were comparable in magnitude to those observed with sildenafil alone in healthy volunteers (see section "Pharmacological properties").

Sildenafil 100 mg did not affect the pharmacokinetic parameters of HIV protease inhibitors saquinavir and ritonavir, which are CYP3A4 substrates.

In healthy male volunteers, administration of sildenafil at steady state (80 mg three times daily) increased AUC and Cmax of bosentan (125 mg twice daily) by 49.8% and 42%, respectively.

Adding a single dose of sildenafil to sacubitril/valsartan at steady state in patients with arterial hypertension was associated with a significantly greater reduction in blood pressure compared to sacubitril/valsartan alone. Therefore, caution should be exercised when initiating sildenafil in patients receiving treatment with sacubitril/valsartan.

Special precautions for use.

Before initiating therapy, a medical history should be obtained and a physical examination performed to diagnose erectile dysfunction and determine its possible causes.

Cardiovascular risk factors. Since sexual activity carries a certain cardiovascular risk, physicians must assess the cardiovascular status of patients before initiating any treatment for erectile dysfunction. Sildenafil has vasodilatory effects, resulting in mild and transient reduction in blood pressure (see section "Pharmacodynamics"). Before prescribing sildenafil, physicians should carefully consider whether such an effect might adversely affect patients with underlying cardiovascular conditions, especially in combination with sexual activity. Patients who are particularly sensitive to vasodilators include those with left ventricular outflow tract obstruction (e.g., aortic stenosis, hypertrophic obstructive cardiomyopathy) and patients with the rare multisystem atrophy syndrome, one of the manifestations of which is severe autonomic regulation of arterial blood pressure.

Sildenafil potentiates the hypotensive effect of nitrates (see section "Contraindications").

In the post-marketing period, serious adverse cardiovascular events have been reported, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, arterial hypertension, and arterial hypotension, which temporally coincided with sildenafil use. In most patients, but not all, there were underlying cardiovascular risk factors. Many of these adverse events occurred during or immediately after sexual intercourse, and only a few occurred shortly after sildenafil administration without sexual activity. Therefore, it is not possible to determine whether the occurrence of such adverse reactions is directly related to risk factors or whether their development is caused by other factors.

Priapism. Medications for the treatment of erectile dysfunction, including sildenafil, should be used with caution in patients with anatomical penile deformity (e.g., angulation, cavernous fibrosis, or Peyronie’s disease) or in patients with conditions that may predispose to priapism (sickle cell anemia, multiple myeloma, or leukemia).

Since sildenafil became available on the market, cases of prolonged erection and priapism have been reported. If an erection lasts longer than 4 hours, patients should seek immediate medical help. Without prompt treatment, priapism may lead to penile tissue damage and permanent loss of erectile function.

Concomitant use with other PDE-5 inhibitors or other medications for erectile dysfunction. The safety and efficacy of concomitant use of sildenafil with other PDE-5 inhibitors or other medications for pulmonary arterial hypertension containing sildenafil, or with other medications for erectile dysfunction, have not been studied. Therefore, such combinations are not recommended.

Effect on vision. Spontaneous reports of visual disturbances have been associated with the use of sildenafil and other PDE-5 inhibitors (see section "Adverse reactions"). Spontaneous reports and data from observational studies have indicated cases of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition, associated with the use of sildenafil and other PDE-5 inhibitors (see section "Adverse reactions"). Patients should be advised that if sudden visual impairment occurs, use of ERGOS® should be discontinued and immediate medical advice sought (see section "Contraindications").

Concomitant use with ritonavir. Concomitant use of sildenafil and ritonavir is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Concomitant use with α-adrenoreceptor blockers. Sildenafil should be used with caution in patients taking α-adrenoreceptor blockers, as this combination may lead to symptomatic hypotension in some susceptible patients. Symptomatic hypotension usually occurs within 4 hours after sildenafil administration. To minimize the potential for postural hypotension in patients taking α-adrenoreceptor blockers, their condition should first be stabilized with α-blocker therapy before initiating sildenafil treatment. Additionally, consideration should be given to starting with a dose of 25 mg (see section "Dosage and administration"). Patients should also be informed about appropriate actions to take if symptoms of orthostatic hypotension occur.

Effect on bleeding. In vitro studies on human platelets have shown that sildenafil potentiates the anti-aggregatory effect of sodium nitroprusside. There is no information on the safety of sildenafil use in patients with bleeding disorders or acute peptic ulcer. Therefore, sildenafil use in these patient groups should only be considered after careful assessment of the benefit-risk ratio.

After administration of a 100 mg dose to healthy volunteers, no effect on sperm morphology or motility was observed (see section "Pharmacodynamics").

Hearing loss. Physicians should advise patients to discontinue use of ERGOS® and seek immediate medical help if sudden decrease or loss of hearing occurs. These events, which may also be accompanied by tinnitus and dizziness, have been reported in temporal association with PDE-5 inhibitors, including ERGOS®. It is not possible to determine whether these events are directly related to PDE-5 inhibitor use or to other factors.

Concomitant use with antihypertensive agents. Sildenafil exerts systemic vasodilatory effects and may further reduce blood pressure in patients taking antihypertensive medications. In a specific drug interaction study, concomitant oral administration of amlodipine (5 mg or 10 mg) and sildenafil (100 mg) resulted in an average additional reduction in systolic pressure of 8 mm Hg and diastolic pressure of 7 mm Hg.

Sexually transmitted diseases. Use of ERGOS® does not protect against sexually transmitted infections. Consideration should be given to informing patients about necessary preventive measures to protect against sexually transmitted diseases, including human immunodeficiency virus (HIV).

The product contains lactose. It should not be used in men with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

The product contains sucrose. If a sugar intolerance has been diagnosed, patients should consult their physician before using this medication.

The product contains the dye E 102, which may cause allergic reactions when used.

Use during pregnancy or breastfeeding.

ERGOS® is not intended for use in women.

Ability to affect reaction speed while driving or operating machinery.

No studies on the effect of the drug on the ability to drive vehicles or operate machinery have been conducted. Since dizziness and visual disturbances have been reported during clinical trials with sildenafil, patients should determine their individual response to ERGOS® before driving a vehicle or operating machinery.

Method of Administration and Dosage

The medication is administered orally.

Adults. The recommended dose of ERGOS® is 50 mg, taken as needed approximately one hour before sexual activity. Depending on the efficacy and tolerability of the medication, the dose may be increased to 100 mg or decreased to 25 mg* in tablets. The maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once daily. When the medication is taken with food, its effect may occur later compared to administration on an empty stomach.

Elderly patients. Dose adjustment is not required for elderly patients (≥ 65 years of age).

Patients with renal impairment. For patients with mild to moderate renal impairment (creatinine clearance 30–80 mL/min), the recommended dose is the same as stated above under "Adults."

In patients with severe renal impairment (creatinine clearance < 30 mL/min), sildenafil clearance is reduced; therefore, a starting dose of 25 mg* should be considered. Depending on efficacy and tolerability, the dose may be gradually increased if necessary to 50 mg and then to 100 mg.

Patients with hepatic impairment. In patients with hepatic impairment (e.g., cirrhosis), sildenafil clearance is reduced; therefore, a starting dose of 25 mg* should be considered. Depending on efficacy and tolerability, the dose may be gradually increased if necessary to 50 mg and then to 100 mg.

Patients taking other medicinal products. If patients are concurrently using CYP3A4 inhibitors (except ritonavir, which is not recommended to be used concomitantly with sildenafil; see sections "Interaction with other medicinal products and other forms of interactions" and "Special precautions for use"), a starting dose of 25 mg* should be considered.

To minimize the potential risk of postural hypotension in patients taking α-adrenoreceptor blockers, such patients should be stabilized on α-adrenoreceptor blockers prior to initiating sildenafil therapy. Additionally, a starting dose of 25 mg* should be considered (see sections "Interaction with other medicinal products and other forms of interactions" and "Special precautions for use").

*Administer the medicinal product at the appropriate dosage strength.

Children.

The medication is not indicated for use in individuals under 18 years of age.

Overdose.

During clinical trials involving volunteers, administration of single sildenafil doses up to 800 mg resulted in adverse reactions similar to those observed with lower sildenafil doses, but occurring more frequently and with greater severity. Administration of sildenafil at a dose of 200 mg did not increase efficacy but led to a higher incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).

In case of overdose, standard supportive measures should be implemented as needed. Hemodialysis is unlikely to accelerate sildenafil clearance due to the high degree of plasma protein binding and the absence of urinary elimination of sildenafil.

Adverse Reactions

The most commonly reported adverse reactions in clinical trials among patients receiving sildenafil were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, hot flushes, visual disturbances, cyanopsia, and blurred vision. Information on adverse reactions from post-marketing surveillance of sildenafil use has been collected over more than 10 years. Listed below are all clinically significant adverse reactions observed during clinical trials of sildenafil with an incidence higher than that observed with placebo, categorized by system organ class and frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000).

Also included is the frequency of clinically significant adverse reactions reported from post-marketing experience as unknown.

Within each frequency group, adverse effects are listed in decreasing order of severity.

Infections and infestations

Uncommon: Rhinitis.

Immune system disorders

Uncommon: Hypersensitivity.

Nervous system disorders

Very common: Headache.

Common: Dizziness.

Uncommon: Somnolence, hypaesthesia.

Rare: Stroke, transient ischaemic attack, seizures*, seizure recurrence*, syncope.

Eye disorders

Common: Colour vision disorders**, visual disturbances, blurred vision.

Uncommon: Lacrimation disorders***, eye pain, photophobia, photopsia, eye hyperaemia, brightness of vision, conjunctivitis, conjunctival hyperaemia, eye irritation, abnormal sensations in the eye, eyelid oedema, scleral discolouration.

Rare: Non-arteritic anterior ischaemic optic neuropathy*, retinal vessel occlusion*, retinal haemorrhage, arteriosclerotic retinopathy, retinal disorders, glaucoma, visual field defects, diplopia, decreased visual acuity, myopia, asthenopia, floaters, iris disorders, mydriasis, halos around light sources in the visual field, eye swelling, eye puffiness, eye disorders, conjunctival hyperaemia, eye irritation, abnormal sensations in the eye, eyelid oedema, scleral discolouration.

Ear and labyrinth disorders

Uncommon: Dizziness, tinnitus.

Rare: Deafness.

Cardiac disorders

Uncommon: Tachycardia, palpitations.

Rare: Sudden cardiac death*, myocardial infarction, ventricular arrhythmia*, atrial fibrillation, unstable angina.

Vascular disorders

Common: Facial flushing, hot flushes.

Uncommon: Hypertension, hypotension.

Respiratory, thoracic and mediastinal disorders

Common: Nasal congestion.

Uncommon: Epistaxis, nasal sinus congestion.

Rare: Throat tightness, nasal mucosal oedema, nasal dryness.

Gastrointestinal disorders

Common: Nausea, dyspepsia.

Uncommon: Gastroesophageal reflux disease, vomiting, upper abdominal pain, dry mouth.

Rare: Oral hypaesthesia.

Skin and subcutaneous tissue disorders

Uncommon: Rash.

Rare: Stevens-Johnson syndrome*, toxic epidermal necrolysis*.

Musculoskeletal and connective tissue disorders

Uncommon: Myalgia, limb pain.

Renal and urinary disorders

Uncommon: Haematuria.

Reproductive system and breast disorders

Rare: Penile haemorrhage, priapism*, haemospermia, prolonged erection.

General disorders and administration site conditions

Uncommon: Chest pain, increased fatigue, feeling of warmth.

Rare: Irritation.

Investigations

Uncommon: Increased heart rate.

* Reported only during post-marketing surveillance.

** Colour vision disorders: chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia.

*** Lacrimation disorders: dry eyes, lacrimation disorder, increased lacrimation.

The following events were observed in < 2% of patients during controlled clinical trials of sildenafil; a causal relationship has not been established. Reports included events with a probable relationship to the use of the drug. Events not listed were mild and reported too imprecisely to be of significance.

General: Facial oedema, photosensitivity reactions, shock, asthenia, pain, sudden fall, abdominal pain, sudden injury.

Cardiovascular system: Angina pectoris, AV block, migraine, postural hypotension, myocardial ischaemia, cerebral vessel thrombosis, sudden cardiac arrest, ECG abnormalities, cardiomyopathy.

Gastrointestinal tract: Glossitis, colitis, dysphagia, gastritis, gastroenteritis, oesophagitis, stomatitis, abnormal liver function tests, rectal haemorrhage, gingivitis.

Blood and lymphatic system disorders: Anaemia, leucopenia.

Metabolism and nutrition disorders: Thirst, oedema, gout, unstable diabetes, hyperglycaemia, peripheral oedema, hyperuricaemia, hypoglycaemia, hypernatraemia.

Musculoskeletal system: Arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis.

Nervous system: Ataxia, neuralgia, neuropathy, paraesthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes.

Respiratory system: Asthma, dyspnoea, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation, increased cough.

Skin: Urticaria, herpes, pruritus, increased sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.

Special senses: Sudden decrease or loss of hearing, ear pain, eye haemorrhage, cataract, dry eyes.

Urogenital system: Cystitis, nocturia, increased frequency of urination, breast enlargement, urinary incontinence, ejaculation disorder, genital oedema, anorgasmia.

Post-marketing experience. As these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events were reported due to their severity, frequency of reporting, lack of clear alternative explanation, or a combination of these factors.

Cardiovascular and cerebrovascular events. Serious cardiovascular, cerebrovascular, and vascular events have been reported, including cerebral haemorrhage, subarachnoid haemorrhage, intracerebral haemorrhage, and pulmonary haemorrhage, which occurred in temporal association with sildenafil use. Most, but not all, patients had underlying cardiovascular risk factors. Many of these events occurred during or immediately after sexual activity, and several occurred shortly after sildenafil use without sexual activity. Others occurred within hours or days after sildenafil use and sexual activity. It is not possible to determine whether these events are related to the use of the drug, sexual activity, underlying risk factors, a combination of these factors, or other factors.

Blood and lymphatic system: Vaso-occlusive crisis. In a small, prematurely terminated study of Revatio (sildenafil) in patients with pulmonary arterial hypertension secondary to sickle cell anaemia, vaso-occlusive crises requiring hospitalization were reported more frequently with sildenafil than with placebo. The clinical significance of this information for patients taking sildenafil for the treatment of erectile dysfunction is unknown.

Nervous system: Anxiety, transient global amnesia.

Special senses.

Hearing. Since market release, cases of sudden decrease or loss of hearing temporally associated with sildenafil use have been reported. In some cases, medical conditions and other factors that could have contributed to the development of hearing-related adverse reactions were reported. In many cases, follow-up medical information is lacking. It is not possible to determine whether these events are directly related to drug use, underlying risk factors for hearing loss, a combination of these factors, or other factors.

Vision: transient vision loss, eye redness, eye burning, increased intraocular pressure, retinal oedema, retinal vascular disorders or haemorrhage, vitreous detachment.

Rare cases of non-arteritic anterior ischaemic optic neuropathy (NAION), leading to vision loss including permanent vision loss, have been reported in temporal association with PDE-5 inhibitors, including sildenafil. Many, but not all, patients had underlying anatomical or vascular risk factors for NAION, including (but not limited to): small cup-to-disc ratio (crowded optic disc), age over 50 years, hypertension, coronary artery disease, hyperlipidaemia, and smoking. It is not possible to determine whether these events are directly related to PDE-5 inhibitor use, underlying anatomical or vascular risk factors, a combination of all these factors, or other factors.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals should report any suspected adverse reactions in accordance with regulatory requirements.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of the reach of children.

Packaging.

1, 2, or 4 tablets in a blister; 1 blister per carton; 4 tablets in a blister; 2 blisters per carton.

Prescription category. Prescription only.

Manufacturer.

LLC "Pharmaceutical Company "FarCoS".

Manufacturer's address and location of operations.

360, Sviato-Pokrovska St., smt. Hostomel, Irpin, Kyiv Oblast, 08290, Ukraine.