Instructions for Eroton tablets 100mg No. 8
Composition
active ingredient: sildenafil;
1 tablet contains sildenafil citrate in doses equivalent to 50 mg or 100 mg of sildenafil;
excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, copovidone, colloidal anhydrous silicon dioxide, talc, magnesium stearate, croscarmellose sodium, potato starch.
Dosage form
Pills.
Main physicochemical properties: white, biconvex, hexagonal tablets (HEXAGON shape), marked "F" on both sides.
Pharmacotherapeutic group
Drugs used for erectile dysfunction. Sildenafil. ATX code G04B E03.
Pharmacological properties
Pharmacodynamics
Mechanism of action: Sildenafil is an oral medication used to treat erectile dysfunction in men. During sexual arousal, the drug restores diminished erectile function by increasing blood flow to the penis.
The physiological mechanism that causes an erection involves the release of nitric oxide (NO) in the corpora cavernosa during sexual arousal. The released nitric oxide activates the enzyme guanylate cyclase, which stimulates an increase in cyclic guanosine monophosphate (cGMP), which in turn causes relaxation of the smooth muscle of the corpora cavernosa, facilitating blood flow.
Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for the breakdown of cGMP. The effects of sildenafil on erection are peripheral in nature. Sildenafil does not have a direct relaxant effect on isolated human corpus cavernosum, but it potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, sildenafil's inhibition of PDE5 leads to an increase in cGMP levels in the corpus cavernosum. Thus, sexual arousal is required for sildenafil to produce the desired pharmacological effect.
Pharmacodynamic effects. In vitro studies have shown that sildenafil is selective for PDE5, which is actively involved in the erection process. The effect of sildenafil on PDE5 is more potent than on other known phosphodiesterases. This effect is 10 times more potent than the effect on PDE6, which is involved in photoconversion processes in the retina. When using the maximum recommended doses, the selectivity of sildenafil for PDE5 is 80 times higher than its selectivity for PDE1, 700 times higher than for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10 and PDE11. In particular, the selectivity of sildenafil for PDE5 is 4000 times higher than its selectivity for PDE3 - a cAMP-specific isoform of phosphodiesterase involved in the regulation of cardiac contractility.
Pharmacokinetics
Absorption: Sildenafil is rapidly absorbed. Peak plasma concentrations are reached within 30–120 minutes (median 60 minutes) after oral administration in the fasted state. The mean absolute oral bioavailability is 41% (range 25–63%). Over the recommended dose range (25–100 mg), sildenafil AUC and Cmax increase in proportion to dose after oral administration.
When sildenafil is taken with food, the extent of absorption is reduced with a mean prolongation of Tmax to 60 minutes and a mean decrease in Cmax by 29%.
Distribution. The mean steady-state volume of distribution (Vd) is 105 liters, indicating distribution of the drug into body tissues. After a single oral dose of 100 mg sildenafil, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/ml (the coefficient of variation is 40%). Since the binding of sildenafil and its main N-desmethyl metabolite to plasma proteins reaches 96%, the mean maximum plasma concentration of free sildenafil reaches 18 ng/ml (38 nmol). The degree of binding to plasma proteins does not depend on the total concentrations of sildenafil.
In healthy volunteers who used sildenafil once at a dose of 100 mg, less than 0.0002% (average 188 ng) of the administered dose was detected in the ejaculate after 90 minutes.
Biotransformation. Sildenafil is metabolized primarily by the hepatic microsomal isoenzymes CYP3A4 (major pathway) and CYP2C9 (minor pathway). The major circulating metabolite is formed by N-demethylation of sildenafil. The selectivity of the metabolite for PDE5 is comparable to that of sildenafil, and the activity of the metabolite for PDE5 is approximately 50% of that of the parent compound. Plasma concentrations of this metabolite are approximately 40% of those of sildenafil in plasma. The N-demethylated metabolite undergoes further metabolism and has a half-life of approximately 4 hours.
Elimination: The total clearance of sildenafil is 41 l/h, resulting in a half-life of 3-5 hours. After both oral and intravenous administration, sildenafil is excreted as metabolites primarily in the feces (approximately 80% of the administered oral dose) and to a lesser extent in the urine (approximately 13% of the administered oral dose).
Elderly patients: In healthy elderly volunteers (aged 65 years and older), a decrease in sildenafil clearance was observed, which resulted in an increase in plasma concentrations of sildenafil and its active N-demethylated metabolite by approximately 90% compared with the corresponding concentrations in healthy younger volunteers (18-45 years). Due to age-related differences in plasma protein binding, the corresponding increase in plasma concentrations of free sildenafil was approximately 40%.
Renal impairment. In volunteers with mild to moderate renal impairment (creatinine clearance 30–80 ml/min), sildenafil pharmacokinetics were unchanged after a single oral dose of 50 mg. The mean AUC and Cmax of the N-desmethyl metabolite were increased by a maximum of 126% and a maximum of 73%, respectively, compared with those in age-matched volunteers without renal impairment. However, due to high interindividual variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance below 30 ml/min), sildenafil clearance was reduced, resulting in an average increase in AUC and Cmax of 100% and 88%, respectively, compared with age-matched volunteers without renal impairment. In addition, the AUC and Cmax values of the N-demethylated metabolite were significantly increased by 79% and 200%, respectively.
Hepatic impairment: In volunteers with mild to moderate liver cirrhosis (Child-Pugh class A and B), sildenafil clearance was reduced, resulting in increased AUC (84%) and Cmax (47%) compared to age-matched volunteers without hepatic impairment. The pharmacokinetics of sildenafil in patients with severe hepatic impairment have not been studied.
Indication
The drug is recommended for use in men with erectile dysfunction, which is defined as the inability to achieve or maintain a penile erection necessary for successful sexual intercourse.
Sexual arousal is necessary for the drug to be effective.
Contraindication
Hypersensitivity to sildenafil or any of the excipients of the drug.
Concomitant use with nitric oxide donors (such as amyl nitrite) or nitrates in any form - sildenafil has an effect on nitric oxide/cyclic guanosine monophosphate (cGMP) metabolic pathways and potentiates the hypotensive effect of nitrates.
The 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 4.5).
Conditions in which sexual activity is undesirable (severe cardiovascular disorders such as unstable angina or severe heart failure).
The drug is contraindicated in patients who have lost vision in one eye due to non-arteritic anterior ischemic optic neuropathy, regardless of whether this pathology is associated with previous use of PDE5 inhibitors or not.
The presence of diseases such as severe liver dysfunction, arterial hypotension (blood pressure below 90/50 mm Hg), recent stroke or myocardial infarction, and hereditary degenerative retinal diseases such as retinitis pigmentosa (such patients may have genetic disorders of retinal phosphodiesterases) - the safety of sildenafil has not been studied in such subgroups of patients.
Interaction with other medicinal products and other types of interactions
Effects of other drugs 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 decrease sildenafil clearance, and inducers of these isoenzymes may increase sildenafil clearance.
In vivo studies: Population pharmacokinetic analysis of clinical trial data has shown a decrease in sildenafil clearance when co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although no increase in adverse events was observed when sildenafil was co-administered with CYP3A4 inhibitors, a starting dose of 25 mg sildenafil should be considered.
Co-administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at a steady-state dose (1200 mg 3 times daily) with sildenafil (100 mg once daily) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil systemic exposure (AUC). Sildenafil had no effect on the pharmacokinetics of saquinavir (see section 4.2). More potent CYP3A4 inhibitors such as ketoconazole and itraconazole are expected to have a greater effect.
When sildenafil (100 mg once) and erythromycin, a moderate CYP3A4 inhibitor, were administered at steady state (500 mg twice daily for 5 days), a 182% increase in sildenafil systemic exposure (AUC) was observed. In healthy male volunteers, there was no effect of azithromycin (500 mg daily for 3 days) on the AUC, Cmax, Tmax, elimination rate constant, and subsequent half-life of sildenafil or its major circulating metabolite. Cimetidine (a cytochrome P450 inhibitor and nonspecific CYP3A4 inhibitor) at a dose of 800 mg when co-administered with sildenafil at a dose of 50 mg in healthy volunteers resulted in a 56% increase in plasma concentrations of sildenafil.
Grapefruit juice is a weak inhibitor of CYP3A4 in the intestinal wall and may cause a modest increase in plasma levels of sildenafil.
Single administration of antacids (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil.
Although specific drug interaction studies have not been conducted, population pharmacokinetic analysis suggests that sildenafil pharmacokinetics were not altered by concomitant use of drugs belonging to the CYP2C9 inhibitor group (tolbutamide, warfarin, phenytoin), CYP2D6 inhibitor group (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, loop and potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, β-adrenoceptor antagonists, or inducers of CYP450 metabolism (such as rifampicin, barbiturates).
Co-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% decrease in sildenafil AUC and Cmax, respectively. Therefore, concomitant administration of potent CYP3A4 inducers such as rifampin may result in a more pronounced decrease in sildenafil plasma concentrations.
Nicorandil is a hybrid of a calcium channel activator and a nitrate. The nitrate component makes it possible for it to have a serious interaction with sildenafil.
Effects of sildenafil on other drugs.
In vitro studies: Sildenafil is a weak inhibitor of cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 μM). Since peak plasma concentrations of sildenafil are approximately 1 μM, the drug is unlikely to affect the clearance of substrates of these isoenzymes.
There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline and dipyridamole.
In vivo studies: Since sildenafil is known to affect nitric oxide/cyclic guanosine monophosphate (cGMP) metabolism, sildenafil has been shown to potentiate the hypotensive effect of nitrates, and its concomitant use with nitric oxide donors or nitrates in any form is contraindicated (see section 4.3).
Riociguat. Preclinical studies have shown an additive systemic blood pressure lowering effect when PDE5 inhibitors are co-administered with riociguat. Clinical studies have shown that riociguat potentiates the hypotensive effect of PDE5 inhibitors. No beneficial clinical effect was observed in patients who participated in the study from the co-administration of PDE5 inhibitors with riociguat. The concomitant use of riociguat with PDE5 inhibitors (including sildenafil) is contraindicated (see section 4.3).
No significant interactions were observed with the concomitant use of sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg), which are 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 mean maximum blood ethanol levels of 80 mg/dL.
In patients taking sildenafil, no differences in the side effect profile compared to placebo were observed when such classes of antihypertensive drugs as diuretics, β-blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive drugs (vasodilators and centrally acting), adrenergic neurone blockers, calcium channel blockers and α-adrenergic blockers were used concomitantly. In a specific interaction study, when sildenafil (100 mg) was co-administered with amlodipine in patients with arterial hypertension, an additional reduction in supine systolic blood pressure of 8 mm Hg was observed. 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 5.1).
Sildenafil at a dose of 100 mg did not affect the pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, which are CYP3A4 substrates.
In healthy male volunteers, the use of sildenafil at steady state (80 mg twice daily) resulted in an increase in the AUC and Cmax of bosentan (125 mg twice daily) by 49.8% and 42%, respectively.
Application features
Before starting therapy, the patient's medical history should be collected and a physical examination should be performed to diagnose erectile dysfunction and determine its possible causes.
Cardiovascular risk factors. Since sexual activity carries a certain cardiac risk, the physician should assess the patient's cardiovascular status before initiating any treatment for erectile dysfunction. Sildenafil has a vasodilating effect, manifested by a mild and transient decrease in blood pressure (see section "Pharmacodynamics"). Before prescribing sildenafil, the physician should carefully consider whether this effect may adversely affect patients with certain underlying diseases, especially in combination with sexual activity. Patients with increased sensitivity to vasodilators include patients with obstruction of the outflow tract of the left ventricle (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy) or patients with the rare syndrome of multiple system atrophy, one of the manifestations of which is severe dysregulation of blood pressure by the autonomic nervous system.
The drug potentiates the hypotensive effect of nitrates (see the "Contraindications" section).
In the post-marketing period, serious adverse reactions from the cardiovascular system, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic attack, hypertension and hypotension, have been reported in association with sildenafil use. Most patients had risk factors for cardiovascular disease. Many of these adverse reactions occurred during or immediately after sexual intercourse, and only a few occurred shortly after sildenafil use in the absence of sexual activity. Therefore, it is not possible to determine whether the development of these adverse reactions is directly related to the risk factors or whether their development is due to other factors.
Priapism: Erectile dysfunction drugs, including sildenafil, should be prescribed with caution in patients with anatomical deformities of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease) and in patients with conditions predisposing to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
Cases of prolonged erection and priapism have been reported since sildenafil was marketed. If an erection lasts longer than 4 hours, patients should seek immediate medical attention. If not treated promptly, priapism can lead to penile tissue damage and permanent loss of potency.
Effects on vision: There have been spontaneous reports of visual defects with sildenafil and other PDE5 inhibitors (see section 4.8). From spontaneous reports and observational studies, rare cases of non-arteritic anterior ischemic optic neuropathy have been reported with sildenafil and other PDE5 inhibitors (see section 4.8). Patients should be advised that in the event of sudden visual impairment, sildenafil should be discontinued and medical advice should be sought immediately (see section 4.8).
Concomitant use with ritonavir: Concomitant use of sildenafil and ritonavir is not recommended (see section 4.5).
Concomitant use with α-adrenergic blockers. Sildenafil should be used with caution in patients taking α-adrenergic blockers, as the combination may lead to symptomatic hypotension in some susceptible patients. Symptomatic hypotension usually occurs within 4 hours of sildenafil administration. To minimise the risk of postural hypotension in patients taking α-adrenergic blockers, they should be stabilised with α-adrenergic blockers before starting sildenafil. A starting dose of 25 mg should also be considered (see section 4.2). Patients should also be advised what to do if they experience symptoms of orthostatic hypotension.
Effects on bleeding. Studies in human platelets have shown that sildenafil potentiates the antiplatelet effects of sodium nitroprusside in vitro. There is no information on the safety of sildenafil in patients with coagulation disorders or acute peptic ulcer. Therefore, sildenafil should only be used in these patients after careful consideration 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 5.1).
Hearing loss. Physicians should advise patients to discontinue use of PDE5 inhibitors, including this medicinal product, and to seek immediate medical attention if they experience sudden hearing loss or hearing loss. These events, which may also be accompanied by tinnitus and dizziness, have been reported in temporal association with the use of PDE5 inhibitors, including sildenafil. It is not possible to determine whether these events are directly related to the use of PDE5 inhibitors or to other factors.
Concomitant use with antihypertensive drugs. The drug has a systemic vasodilator effect and may further reduce blood pressure in patients taking antihypertensive drugs. In a separate drug interaction study, concomitant administration of amlodipine (5 mg or 10 mg) and sildenafil (100 mg) orally resulted in a mean 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. Patients should be advised of the necessary precautions to protect against sexually transmitted diseases, including human immunodeficiency virus.
Use during pregnancy or breastfeeding
The medicine is not intended for use by women.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
Eroton® may have a minor influence on the ability to drive and use machines.
Studies on the effect of the drug on the ability to drive and use machines have not been conducted. Since dizziness and visual disturbances were reported in clinical studies with sildenafil, patients should be advised to assess their individual response to the drug before driving or operating machinery.
Method of administration and doses
The drug should be administered orally.
Adults. The recommended dose of the drug is 50 mg, to be used if necessary approximately 1 hour before sexual activity. Depending on the effectiveness and tolerability of the drug, the dose can be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The frequency of use of the maximum recommended dose of the drug is 1 time per day. When the drug is used with food, the effect of the drug may occur later than when it is used on an empty stomach.
Elderly patients: No dose adjustment is required for elderly patients (≥ 65 years).
Since sildenafil clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 ml/min), a dose of 25 mg should be considered. Depending on efficacy and tolerability, the dose may be increased gradually to 50 mg and 100 mg if necessary.
Patients with hepatic impairment: Since sildenafil clearance is reduced in patients with hepatic impairment (e.g. cirrhosis), a dose of 25 mg should be considered. Depending on efficacy and tolerability, the dose may be increased gradually to 50 mg and 100 mg if necessary.
Patients taking other medicinal products: If patients are taking CYP3A4 inhibitors concomitantly (see section 4.5), a starting dose of 25 mg should be considered (except for ritonavir, the concomitant use of which with sildenafil is not recommended, see section 4.4).
To minimise the risk of postural hypotension in patients taking α-adrenergic blockers, their condition should be stabilised with α-adrenergic blockers before starting sildenafil. A starting dose of 25 mg should also be considered (see sections 4.4 and 4.5).
When prescribing sildenafil at a dose of 25 mg, use the drug in the appropriate dosage or dosage form.
Children
The medicine is not indicated for use in persons under the age of 18.
Overdose
When using a single dose of sildenafil up to 800 mg, adverse reactions were similar to those observed with lower doses of sildenafil, but were more frequent and more severe. The use of sildenafil at a dose of 200 mg did not lead to increased efficacy, but caused an increase in the number of cases of adverse reactions (headache, hot flashes, dizziness, dyspepsia, nasal congestion, visual disturbances).
In the event of overdose, standard supportive measures should be employed as necessary. Acceleration of sildenafil clearance during hemodialysis is unlikely due to the high degree of binding of the drug to plasma proteins and the lack of elimination of sildenafil in the urine.
Side effects
The most commonly reported adverse reactions were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, hot flushes, visual disturbances, cyanopsia and blurred vision.
All clinically significant adverse reactions observed in clinical trials at an incidence greater than placebo are listed below by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000). In addition, the frequency of clinically significant adverse reactions reported during post-marketing experience is defined as unknown. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Infectious and invasive diseases.
Uncommon: rhinitis.
From the immune system.
Uncommon: hypersensitivity.
From the nervous system.
Very common: headache.
Common: dizziness.
Uncommon: drowsiness, hypoesthesia.
Rare: stroke, transient ischemic attack, seizures*, recurrent seizures*, syncope.
From the organs of vision.
Common: color perception disorders**, visual disturbances, blurred vision.
Uncommon: lacrimation disorder***, eye pain, photophobia, photopsia, ocular hyperemia, visual acuity reduced, conjunctivitis.
Rare: non-arteritic anterior ischemic optic neuropathy*, retinal vascular occlusion*, retinal haemorrhage, arteriosclerotic retinopathy, retinal disorders, glaucoma, visual field defects, diplopia, visual acuity reduced, myopia, asthenopia, floating vitreous opacities, iris disorders, mydriasis, halos, eye oedema, eye swelling, eye disorders, conjunctival hyperaemia, eye irritation, abnormal sensation in eyes, eyelid oedema, sclera discolouration.
From the side of the organs of hearing and vestibular apparatus.
Uncommon: dizziness, tinnitus.
Rare: deafness.
From the heart.
Uncommon: tachycardia, palpitations.
Rare: sudden cardiac death*, myocardial infarction, ventricular arrhythmia*, atrial fibrillation, unstable angina.
From the side of the vessels.
Common: flushing, hot flushes.
Uncommon: hypertension/hypotension.
On the part of the respiratory system, chest and mediastinum.
Common: nasal congestion.
Uncommon: epistaxis, sinus congestion.
Rare: feeling of tightness in the throat, swelling of the nasal mucosa, dry nose.
From the gastrointestinal tract.
Common: nausea, dyspepsia.
Uncommon: gastroesophageal reflux disease, vomiting, upper abdominal pain, dry mouth.
Rare: oral hypoesthesia.
On the skin and subcutaneous tissue.
Uncommon: rash.
Rare: Stevens-Johnson syndrome*, toxic epidermal necrolysis*.
Musculoskeletal and connective tissue disorders.
Uncommon: myalgia, pain in extremity.
From the urinary system.
From the reproductive system and mammary glands.
Rare: penile bleeding, priapism*, hematospermia, prolonged erection.
General disorders.
Uncommon: chest pain, fatigue, feeling hot.
Rare: irritation.
Examination.
Uncommon: increased heart rate.
*Reported only during post-marketing surveillance.
** Color perception disorders: chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia.
*** Lacrimation disorders: dry eyes, lacrimation disorders and lacrimation increased.
The following events occurred in < 2% of patients; causality has not been determined. Reports included events that had a probable relationship to drug use. Events that were mild and reported too imprecisely to be of significance were not included.
General: Facial edema, photosensitivity reactions, shock, asthenia, pain, sudden fall, abdominal pain, sudden injury.
Cardiovascular system: angina pectoris, atrioventricular block, migraine, postural hypotension, myocardial ischemia, cerebral thrombosis, sudden cardiac arrest, ECG abnormalities, cardiomyopathy.
Gastrointestinal: glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, abnormal liver function tests, rectal bleeding, gingivitis.
From the blood and lymphatic system: anemia, leukopenia.
Metabolism and nutrition: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia, hypoglycemia, hypernatremia.
Musculoskeletal system: arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.
Nervous system: ataxia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes.
From the respiratory system: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation, increased cough.
Skin: urticaria, herpes, itching, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.
Specific sensations: sudden decrease or loss of hearing, earache, hemorrhage in the eye, cataract, dry eyes.
From the urogenital system: cystitis, nocturia, increased frequency of urination, breast enlargement, urinary incontinence, ejaculation disorders, swelling of the genitals, anorgasmia.
Post-marketing experience: The following adverse reactions have been identified during post-marketing experience with sildenafil. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency and establish a causal relationship to the drug.
Cardiovascular and cerebrovascular events. Serious cardiovascular, cerebrovascular and vascular events, including cerebrovascular haemorrhage, subarachnoid and intracerebral haemorrhage and pulmonary haemorrhage, have been reported in temporal association with sildenafil use. The majority of patients had pre-existing cardiovascular risk factors. Most of these events have been reported to occur during or shortly after sexual activity, and occasionally these events have occurred immediately after sildenafil use without sexual activity. Occasionally, complications have occurred within hours or days of sildenafil use and sexual activity. It is not possible to determine whether these events are directly related to the drug, to sexual activity, to pre-existing risk factors, or to a combination of these factors or to other factors.
Blood and lymphatic system: Vaso-occlusive crisis. In a small, prematurely terminated study of sildenafil in patients with pulmonary arterial hypertension secondary to sickle cell disease, the incidence of vaso-occlusive crises requiring hospitalization was higher than with placebo. The clinical significance of these findings for patients taking sildenafil for the treatment of erectile dysfunction is unknown.
Nervous system: anxiety, transient global amnesia.
Specific feelings.
Hearing. After the release of the drug
