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

Composition:

Active substance: sildenafil;

1 tablet contains sildenafil citrate equivalent to 50 mg or 100 mg of sildenafil;

Excipients: microcrystalline cellulose, anhydrous dicalcium phosphate, sodium croscarmellose, hypromellose, magnesium stearate; coating Opadry 03K80814 blue: hypromellose, titanium dioxide (E 171), triacetin, indigo carmine (E 132).

Dosage form. Film-coated tablets.

Main physicochemical characteristics: round, biconvex, smooth on both sides, film-coated tablets of blue color.

Pharmacotherapeutic group.

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

Pharmacological Properties.

Pharmacodynamics.

Sildenafil is an oral therapeutic agent used for the treatment of erectile dysfunction in men. Under natural conditions, particularly during sexual stimulation, it restores impaired erectile function by enhancing blood flow to the penis.

The physiological mechanism of penile erection involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO activates the enzyme guanylate cyclase, leading to increased levels of cyclic guanosine monophosphate (cGMP), relaxation of smooth muscles in the corpus cavernosum, and enhanced blood inflow.

Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for cGMP degradation. Sildenafil exerts a peripheral effect on erectile function. Sildenafil does not have a direct relaxant effect on isolated human corpus cavernosum tissue, but it significantly enhances the relaxant effect of NO on this tissue.

During activation of the NO/cGMP pathway, which occurs during sexual stimulation, inhibition of PDE5 by sildenafil leads to increased cGMP levels in the corpus cavernosum. Therefore, sexual stimulation is necessary for sildenafil to exert its required pharmacological effect.

Effect on pharmacodynamics.

In vitro studies have shown that sildenafil is selective for PDE5, which is involved in the erectile process. Its inhibitory effect on PDE5 is stronger than on other known phosphodiesterases. This effect is 10-fold greater than its effect on PDE6, which is involved in phototransduction in the retina. At maximum recommended doses, sildenafil's selectivity for PDE5 is 80 times greater than for PDE1, 700 times greater than for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11. In particular, sildenafil's selectivity for PDE5 is 4000 times greater than for PDE3—a cGMP-specific phosphodiesterase isoform involved in cardiac contractility regulation.

Pharmacokinetics.

Absorption.

Sildenafil is rapidly absorbed. Maximum plasma concentrations (Cmax) are reached within 30–120 minutes (on average, 60 minutes) after oral administration on an empty stomach. The mean absolute bioavailability after oral administration is 41% (range: 25–63%).

After oral administration, AUC and Cmax of sildenafil increase proportionally with dose within the recommended dosage range (25–100 mg). When sildenafil is taken with food, the absorption rate is reduced, resulting in a mean delay in tmax of 60 minutes and a mean reduction in Cmax by 29%.

Distribution.

The mean volume of distribution at steady state (Vd) for sildenafil is 105 L, indicating extensive tissue distribution. After a single 100 mg oral dose, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/mL (coefficient of variation 40%). Since sildenafil (and its major metabolite, N-desmethyl sildenafil, in systemic circulation) is 96% bound to plasma proteins, the mean maximum free sildenafil plasma concentration is about 18 ng/mL (38 nmol). Protein binding is independent of total drug concentration.

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

Metabolism.

Sildenafil is primarily metabolized by hepatic microsomal isoenzymes CYP3A4 (major pathway) and CYP2C9 (minor pathway). The major circulating metabolite is formed via N-demethylation of sildenafil. This metabolite has selectivity for PDE5 comparable to that of sildenafil, and its activity against PDE5 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.

Excretion.

The total systemic clearance of sildenafil is 41 L/h, with a terminal half-life of 3–5 hours. After oral or intravenous administration, sildenafil is excreted mainly as metabolites, predominantly 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

Ageing.

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 (aged 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 of 100% and 88%, respectively, compared to age-matched volunteers with normal renal function. Additionally, AUC and Cmax of the N-desmethyl metabolite increased significantly 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 by 84% and Cmax by 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.

Moginin® is recommended for use in men with erectile dysfunction, defined as the inability to achieve or maintain a penile erection sufficient for successful sexual intercourse.

For Moginin® to be effective, sexual stimulation is required.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
Concomitant use with NO donors (such as amyl nitrite) or nitrates in any form is contraindicated, as sildenafil is known to affect the NO/cyclic guanosine monophosphate (cGMP) pathway and potentiates the hypotensive effect of nitrates (see section "Pharmacological properties").
Concomitant use of PDE5 inhibitors (including sildenafil) with guanylate cyclase stimulators such as riociguat is contraindicated, as it may lead to symptomatic hypotension (see section "Interaction with other medicinal products and other forms of interaction").
Conditions in which sexual activity is not recommended (e.g., severe cardiovascular disorders such as unstable angina or severe heart failure).
Loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy, regardless of whether this condition is associated with prior use of PDE5 inhibitors or not (see section "Special precautions for use").
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), as the safety of sildenafil has not been studied in these patient subgroups.

Interaction with other medicinal products and other forms of interaction.

Effect of other medicinal products on sildenafil

In vitro studies

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

In vivo studies

Reduced sildenafil clearance has been demonstrated when co-administered with CYP3A4 inhibitors (ketoconazole, erythromycin, cimetidine). Although increased frequency of adverse events has not been observed when sildenafil is used concomitantly with CYP3A4 inhibitors, consideration should be given to starting sildenafil 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 twice daily), and sildenafil (single 100 mg dose) resulted in a 300% increase (4-fold) in Cmax and a 1000% increase (11-fold) in plasma AUC of sildenafil. After 24 hours, plasma sildenafil levels were still approximately 200 ng/mL compared to approximately 5 ng/mL when sildenafil was administered alone, indicating a significant effect of ritonavir on a wide 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); under no circumstances should the maximum sildenafil dose 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 systemic exposure (AUC) of sildenafil. No effect of sildenafil on the pharmacokinetics of saquinavir was observed (see section "Dosage and administration"). More potent CYP3A4 inhibitors such as ketoconazole and itraconazole are expected to have a more pronounced effect.

When sildenafil (single 100 mg dose) was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg twice daily for 5 days), an 182% increase in 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 CYP3A4 in the intestinal wall and may cause a moderate increase in plasma levels of sildenafil.

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

Although specific interaction studies with all medicinal products have not been conducted, population pharmacokinetic analysis data indicate that 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-adrenergic receptor antagonists, or CYP450 metabolism inducers (such as rifampicin, barbiturates).

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 sildenafil concentration.

Nicorandil is a hybrid of a potassium channel opener and a nitrate. The nitrate component may lead to a serious interaction with sildenafil.

Effect of sildenafil on other medicinal products

In vitro studies

Sildenafil is a weak inhibitor of cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 (IC50 >150 µmol). Since peak plasma concentrations of sildenafil are approximately 1 µmol, the effect of Moginin® 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 sildenafil is known to affect NO/cGMP metabolism, it has been established that sildenafil potentiates the hypotensive effect of nitrates; therefore, concomitant use with nitric oxide donors or nitrates in any form is contraindicated (see section "Contraindications").

Riociguat. Preclinical studies have demonstrated an additive systemic effect of lowering blood pressure when PDE5 inhibitors are used concomitantly with riociguat. Clinical studies have shown that riociguat enhances the hypotensive effect of PDE5 inhibitors. In patients participating in the study, no positive clinical effect was observed with concomitant use of PDE5 inhibitors and riociguat.

Concomitant use of riociguat with PDE5 inhibitors (including sildenafil) is contraindicated (see section "Contraindications").

Concomitant use of sildenafil and α-adrenergic receptor 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 drug interaction studies, the α-adrenergic receptor blocker 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 had been stabilized with doxazosin. In these populations, mean additional reductions in blood pressure in the supine position were 7/7 mm Hg, 9/5 mm Hg, and 8/4 mm Hg, and mean reductions in blood pressure in the standing position were 6/6 mm Hg, 11/4 mm Hg, and 4/5 mm Hg, respectively.

Cases of symptomatic orthostatic hypotension have been reported with concomitant use of sildenafil and doxazosin in patients whose condition had been stabilized with doxazosin. These reports described episodes of dizziness and pre-syncope, but no syncope.

No significant interactions were observed with concomitant administration of sildenafil (50 mg) and 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 concomitantly using classes of antihypertensive drugs such as diuretics, β-adrenergic receptor blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive drugs (vasodilators and centrally acting), adrenergic neuron blockers, calcium channel blockers, and α-adrenergic receptor 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 reductions in blood pressure 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 the 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 significantly greater blood pressure reduction compared to sacubitril/valsartan alone. Therefore, sildenafil should be initiated with caution in patients receiving 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 potential causes.

Cardiovascular risk factors

Since sexual activity carries a certain cardiovascular risk, physicians should evaluate the cardiovascular status of patients prior to 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, particularly when combined with sexual activity.

Patients who are more sensitive to vasodilators include those with left ventricular outflow tract obstruction (e.g., aortic stenosis, hypertrophic obstructive cardiomyopathy) or patients with the rare multisystem atrophy syndrome, one of the manifestations of which is severe autonomic nervous system dysfunction in blood pressure regulation.

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

Serious cardiovascular adverse reactions, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, arterial hypertension, and arterial hypotension, have been reported in temporal association with sildenafil use. Most of these patients had underlying cardiovascular risk factors. The majority of adverse reactions occurred during or immediately after sexual intercourse, and only a few occurred shortly after taking the drug 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 influenced by other factors.

Priapism

Erectile dysfunction treatments, including sildenafil, should be used with caution in patients with anatomical penile deformity (such as angulation, cavernosal fibrosis, or Peyronie’s disease) or in patients with conditions predisposing to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).

There are reports of prolonged erection and priapism associated with sildenafil use.

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 PDE5 inhibitors or other erectile dysfunction treatments

The safety and efficacy of concomitant use of sildenafil with other PDE5 inhibitors or other pulmonary arterial hypertension treatments containing sildenafil, or with other erectile dysfunction treatments, have not been studied. Therefore, such combinations are not recommended.

Effect on vision

Cases of visual disturbances have been reported in association with sildenafil and other PDE5 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 sildenafil and other PDE5 inhibitors (see section "Adverse reactions"). Patients should be advised to discontinue use of the medicinal product Moginyn® and seek immediate medical attention in case of sudden visual loss (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 individuals (see section "Interaction with other medicinal products and other forms of interaction"). Symptomatic hypotension usually occurs within 4 hours after sildenafil administration. To minimize the potential for postural hypotension, patients taking α-adrenoreceptor blockers should have their condition stabilized on these agents before initiating sildenafil therapy. Consideration should also be given to starting with an initial dose of 25 mg (see section "Method of administration and dosage"). Patients should also be informed about appropriate actions to take if symptoms of orthostatic hypotension occur.

Effect on blood coagulation

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

Effect on spermatozoa

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 PDE5 inhibitors, including the medicinal product Moginyn®, and seek immediate medical attention in case of sudden decrease or loss of hearing. These events, which may also be accompanied by tinnitus and dizziness, have been reported in temporal association with PDE5 inhibitors, including sildenafil. It is not possible to determine whether these events are directly related to PDE5 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. Data show that concomitant oral administration of amlodipine (5 mg or 10 mg) and sildenafil (100 mg) resulted in an average additional reduction in systolic blood pressure of 8 mm Hg and diastolic blood pressure of 7 mm Hg.

Sexually transmitted diseases

Sildenafil does not protect against sexually transmitted diseases. Consideration should be given to informing patients about the need for protective measures to prevent transmission of sexually transmitted infections, including human immunodeficiency virus (HIV).

Excipients

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding

The medicinal product Moginyn® is not intended for use in women.

Ability to affect reaction speed when driving or operating machinery

The medicinal product Moginyn® may have a minor influence on the ability to drive or operate machinery. Since dizziness and visual disturbances have been reported with sildenafil use, patients should determine their individual response to sildenafil before driving a vehicle or operating machinery.

Method of Administration and Dosage

The medicinal product is administered orally.

Adults

The recommended dose of sildenafil is 50 mg, taken as needed approximately one hour before sexual activity. Depending on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg*. The maximum recommended dose is 100 mg.

The maximum recommended dose should not be administered more than once daily. When Moginin® is taken with food, the onset of effect may be delayed compared to administration on an empty stomach (see section "Pharmacokinetics").

Elderly Patients (≥ 65 years of age)

Dose adjustment in elderly patients is not required.

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 for adults.

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

Patients with Hepatic Impairment

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

Patients Taking Other Medicinal Products

If patients are concurrently using CYP3A4 inhibitors (see section "Interaction with Other Medicinal Products and Other Forms of Interaction"), a starting dose of 25 mg* should be considered (except for ritonavir, which is not recommended to be co-administered with sildenafil; see section "Special Warnings and Precautions for Use").

To minimize the potential for postural hypotension in patients taking α-adrenoreceptor blockers, their condition should be stabilized on α-adrenoreceptor blockers prior to initiating sildenafil therapy. A starting dose of 25 mg* should also be considered (see sections "Interaction with Other Medicinal Products and Other Forms of Interaction" and "Special Warnings and Precautions for Use").

* Administer sildenafil at the appropriate dosage strength.

Children

The medicinal product Moginin® is not indicated for use in individuals under 18 years of age.

Overdose

During clinical studies in volunteers, adverse reactions following single doses of sildenafil up to 800 mg were similar to those observed with lower doses but occurred more frequently and were more severe.

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 required. Accelerated clearance of sildenafil by hemodialysis is unlikely due to the high degree of plasma protein binding and lack of urinary elimination of sildenafil.

Side effects.

The safety profile of sildenafil is based on data obtained from 74 double-blind, placebo-controlled clinical trials (9570 patients). The most commonly reported adverse reactions in clinical studies among patients taking sildenafil were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, 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.

Since not all adverse reactions were reported and not all adverse reactions were included in the sildenafil safety database, the frequency of such reactions cannot be reliably determined.

The clinically significant adverse reactions that occurred in clinical trials at a higher frequency than with placebo are listed below by system organ class and frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000).

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

Within each frequency grouping, adverse effects are listed in order of decreasing incidence.

Infections and infestations

Uncommon: rhinitis.

Immune system disorders

Uncommon: hypersensitivity.

Nervous system disorders

Very common: headache.

Common: dizziness.

Uncommon: somnolence, hypoesthesia.

Rare: stroke, transient ischemic attack, seizures*, seizure recurrence*, syncope.

Eye disorders

Common: colour vision disturbance**, visual disturbances, blurred vision.

Uncommon: lacrimation disorders***, eye pain, photophobia, photopsia, eye hyperemia, brightness of vision, conjunctivitis.

Rare: non-arteritic anterior ischemic optic neuropathy*, retinal vessel occlusion*, retinal hemorrhage, arteriosclerotic retinopathy, retinal disorders, glaucoma, visual field defects, diplopia, decreased visual acuity, myopia, asthenopia, floaters, iris disorders, mydriasis, halos around lights in the visual field, eye swelling, eye edema, eye disorders, conjunctival hyperemia, eye irritation, abnormal sensations in the eyes, eyelid edema, scleral discoloration.

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 edema, dryness in the nose.

Gastrointestinal disorders

Common: nausea, dyspepsia.

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

Rare: oral hypoesthesia.

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: hematuria.

Reproductive system and breast disorders

Rare: penile hemorrhage, priapism*, hematospermia, 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 studies.

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

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

The following events were observed in <2% of patients in controlled clinical trials; causal relationship not established. Reports included events with a probable relationship to sildenafil use. Events not listed were mild and reports too imprecise to be meaningful.

General: facial edema, photosensitivity reactions, shock, asthenia, pain, sudden fall, abdominal pain, sudden injury.

Cardiovascular system: angina, AV block, migraine, postural hypotension, myocardial ischemia, cerebral vascular thrombosis, sudden cardiac arrest, ECG abnormalities, cardiomyopathy.

Gastrointestinal tract: glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, abnormal liver function tests, rectal bleeding, gingivitis.

Blood and lymphatic system disorders: anemia, leukopenia.

Metabolism and nutrition disorders: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.

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

Nervous system: ataxia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes.

Respiratory system: asthma, dyspnea, 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 hemorrhage, cataract, dry eyes.

Genitourinary system: cystitis, nocturia, increased urinary frequency, breast enlargement, urinary incontinence, ejaculation disorders, genital swelling, anorgasmia.

Post-marketing experience. The following adverse reactions have been identified during post-marketing use. Because 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 seriousness, 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 hemorrhage, subarachnoid and intracerebral hemorrhage, and pulmonary hemorrhage, temporally associated with sildenafil use. Most patients had underlying cardiovascular risk factors. Most events occurred during or immediately after sexual activity, and several occurred shortly after sildenafil use without sexual activity. Other events occurred within hours or days after sildenafil use and after sexual activity. It is not possible to determine whether these events are related to the drug, sexual activity, underlying risk factors, a combination of these factors, or other factors.

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

Nervous system disorders: anxiety, transient global amnesia.

Special senses

Hearing. 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 hearing-related adverse reactions were present. In many cases, follow-up medical information is lacking. It is not possible to determine whether these events are directly related to sildenafil 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 edema, retinal vascular disorders or hemorrhage, vitreous detachment.

Rarely, cases of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent vision loss, have been reported temporally associated with PDE5 inhibitors, including sildenafil. In many patients, anatomical or vascular risk factors for NAION were present, including (but not limited to): small cup-to-disc ratio (crowded optic disc), age over 50 years, hypertension, coronary artery disease, hyperlipidemia, and smoking. It is not possible to determine whether these events are directly related to PDE5 inhibitor use, underlying anatomical or vascular risk factors, a combination of 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, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of the reach of children.

Packaging.

1 or 4 tablets in a blister; 1 blister in a cardboard package.

Prescription status.

Prescription only.

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and place of business.

SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.