Instructions for use Erosil tablets 100 mg No. 8
Composition
active ingredient: sildenafil;
1 tablet contains sildenafil citrate equivalent to 100% sildenafil 50 mg or 100 mg;
excipients: lactose monohydrate; magnesium gluconate; powdered sugar; calcium stearate; lemon flavoring; tartrazine dye (E 102).
Dosage form
Pills.
Main physicochemical properties: biconvex tablets of yellow or yellow-brown color with interspersed lines on one side.
Pharmacotherapeutic group
Drugs used to treat erectile dysfunction. ATC code G04B E03.
Pharmacological properties
Pharmacodynamics
Mechanism of action: Sildenafil is an oral medication used to treat erectile dysfunction. During sexual arousal, the drug restores impaired 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 NO 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 effect of sildenafil on erection is 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, which occurs during 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 (Cmax) 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), the area under the concentration-time curve (AUC) and Cmax of sildenafil 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 average steady-state volume of distribution (Vd) is 105 l, indicating distribution of the drug into body tissues. After a single oral dose of sildenafil at a dose of 100 mg, the average Cmax 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 average Cmax 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 the activity of the parent compound. The plasma concentration of this metabolite is approximately 40% of the plasma concentration of sildenafil. The N-demethylated metabolite undergoes further metabolism and its half-life is 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 faeces (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 increased by a maximum of 126% and 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 mean increases 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 200% and 79%, 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
Erosil 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.
For Erosil to be effective, sexual arousal is required.
Contraindication
– Hypersensitivity to sildenafil or to other components of the drug.
– Concomitant use with nitric oxide donors (such as amyl nitrite) or nitrates in any form, as sildenafil is known to affect the nitric oxide/cyclic guanosine monophosphate (cGMP) metabolic pathways and potentiate 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 “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 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 known hereditary degenerative retinal diseases 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 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: Data from studies have 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 AUC. Sildenafil did not appear to have an effect on the pharmacokinetics of saquinavir. More potent CYP3A4 inhibitors such as ketoconazole and itraconazole are expected to have a more pronounced effect.
When sildenafil (100 mg once) and erythromycin, a moderate CYP3A4 inhibitor, were used at steady state (500 mg twice daily for 5 days), an increase in sildenafil AUC by 182% 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 an increase in plasma sildenafil concentrations by 56%.
Grapefruit juice is a weak inhibitor of CYP3A4 in the intestinal wall and may cause a modest increase in plasma levels of sildenafil.
Concomitant use of antacids (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil.
Although specific drug interaction studies have not been conducted, there is evidence that the pharmacokinetics of sildenafil were not altered by concomitant use with 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).
In a study in healthy male volunteers, 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, co-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.
Effect 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 μmol). Since peak plasma concentrations of sildenafil are approximately 1 μmol, the effect of Erosil on the clearance of substrates of these isoenzymes is unlikely.
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 have an effect on the metabolism of NO and cGMP, sildenafil has been shown to potentiate the hypotensive effect of nitrates, and its concomitant use with NO donors or nitrates in any form is contraindicated (see section 4.3).
Riociguat. An additive systemic blood pressure lowering effect has been reported when PDE5 inhibitors are co-administered with riociguat. Studies suggest that riociguat potentiates the hypotensive effects of PDE5 inhibitors. No beneficial clinical effect was observed in patients who participated in the study when PDE5 inhibitors were co-administered with riociguat. The concomitant use of riociguat with PDE5 inhibitors, including sildenafil, is contraindicated (see section 4.3).
Concomitant use of sildenafil and α-adrenergic blockers may lead to symptomatic hypotension in some susceptible patients. This reaction most often occurred within 4 hours of sildenafil administration. In a specific drug interaction study, the α-adrenergic blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) were co-administered to patients with benign prostatic hyperplasia who were stabilized on doxazosin. In these populations, mean additional reductions in supine blood pressure of 7/7 mmHg, 9/5 mmHg and 8/4 mmHg and mean reductions in standing blood pressure of 6/6 mmHg, 11/4 mmHg and 4/5 mmHg, respectively, were observed. When sildenafil and doxazosin were used concomitantly in patients stabilized on doxazosin, symptomatic orthostatic hypotension, as well as dizziness and fainting, but without syncope, have been reported occasionally.
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 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 the side effect profile were observed compared to placebo when taking concomitant classes of antihypertensive drugs such as diuretics, β-adrenergic blockers, ACE inhibitors, and angiotensin II antagonists.
angiotensin II receptor blockers, antihypertensive drugs (vasodilators and centrally acting), adrenergic neurone blockers, calcium channel blockers and α-adrenergic blockers. In an interaction study with the simultaneous use of sildenafil (100 mg) and amlodipine in patients with arterial hypertension, an additional decrease in supine systolic blood pressure of 8 mm Hg was observed. The corresponding decrease 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 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, administration of sildenafil at steady state (80 mg 3 times daily) resulted in an increase in the AUC and Cmax of bosentan (125 mg 2 times 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 5.1). 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 left ventricular outflow tract obstruction (e.g. aortic stenosis, hypertrophic obstructive cardiomyopathy) and 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.
Erosil potentiates the hypotensive effect of nitrates (see the "Contraindications" section).
Serious cardiovascular adverse reactions, 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, but not all, patients had cardiovascular risk factors. Many of these adverse reactions occurred during or immediately after sexual intercourse, and only a few occurred shortly after taking Erosil without 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) or 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. If an erection lasts more than 4 hours, patients should seek immediate medical attention. If not treated promptly, priapism can lead to damage to penile tissue and permanent loss of potency.
Concomitant use with other PDE5 inhibitors or other drugs for the treatment of erectile dysfunction. The safety and efficacy of concomitant use of sildenafil with other PDE5 inhibitors or other drugs for the treatment of pulmonary arterial hypertension that contain sildenafil (e.g. Revatio), or with other drugs for the treatment of erectile dysfunction have not been studied. Therefore, the use of such combinations is not recommended.
Effects on vision. There have been isolated reports of visual defects associated with the use of sildenafil and other PDE5 inhibitors (see section "Adverse reactions"). Cases of non-arteritic anterior ischemic optic neuropathy, a rare condition, have been spontaneously reported and reported in an observational study as associated with the use of sildenafil and other PDE5 inhibitors (see section "Adverse reactions"). Patients should be warned that in the event of sudden visual impairment, the use of Erosil should be discontinued and a doctor should be consulted immediately (see section "Contraindications").
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 minimize the potential for postural hypotension in patients taking α-adrenergic blockers, patients should be stabilized with α-adrenergic blockers before starting sildenafil. A starting dose of 25 mg should also be considered. Patients should also be instructed on how to respond to symptoms of orthostatic hypotension.
Effects on bleeding. Studies in human platelets have shown that sildenafil potentiates the antiaggregatory 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.
Erosil contains lactose and should not be used in men with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
After administration of a dose of 100 mg 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 Erosil, and 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 Erosil. 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. Sildenafil has a systemic vasodilator effect and may further reduce blood pressure in patients taking antihypertensive drugs. In a drug interaction study, concomitant administration of amlodipine (5 mg or 10 mg) and oral sildenafil (100 mg) 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. The use of Erosil does not protect against sexually transmitted diseases. Consideration should be given to informing patients about the necessary precautions to protect against sexually transmitted diseases, including human immunodeficiency virus.
Use during pregnancy or breastfeeding
Erosil is not intended for use by women.
Ability to influence reaction speed when driving vehicles or other mechanisms
Erosil may have a minor influence on the ability to drive or use machines. Since dizziness and visual disturbances have been reported in studies with sildenafil, patients should be advised to assess their individual response to Erosil before driving or operating machinery.
Method of administration and doses
The drug is administered orally.
Adults. The recommended dose of Erosil is 50 mg and is used if necessary approximately one 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 using Erosil with food, the effect of the drug may occur later than when used on an empty stomach.
Elderly patients: No dose adjustment is required for elderly patients (≥ 65 years).
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 given above in the Adults section.
Since in patients with severe renal insufficiency (creatinine clearance
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.
To minimise the potential for postural hypotension in patients taking α-adrenergic blockers, patients should be stabilised on α-adrenergic blockers before starting sildenafil. A starting dose of 25 mg should also be considered (see sections 4.5 and 4.4).
Children.
The drug is not indicated for use in patients under 18 years of age.
Overdose
In studies involving volunteers, when using a single dose of sildenafil up to 800 mg, adverse reactions were similar to those observed with the use of sildenafil in lower doses, but were more frequent and more severe. The use of sildenafil in a dose of 200 mg did not lead to increased efficacy, but caused an increase in the number of cases of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).
In case of overdose, usual 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.
Adverse reactions
The most commonly reported adverse reactions were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, hot flushes, visual disturbances, cyanopsia and blurred vision.
Adverse reactions are listed below by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 -
Infections and infestations: uncommon – rhinitis.
Immune system disorders: uncommon – hypersensitivity.
Nervous system disorders: very common - headache; common - dizziness; uncommon - drowsiness, hypoesthesia; rare - stroke, transient ischemic attack, convulsions*, recurrent convulsions*, syncope.
On the part of the organs of vision: often - color perception disorders**, visual disorders, blurred vision; infrequently - lacrimation disorders***, eye pain, photophobia, photopsia, ocular hyperemia, visual brightness, conjunctivitis; rarely - non-arteritic anterior ischemic optic neuropathy*, retinal vascular occlusion*, retinal hemorrhage, arteriosclerotic retinopathy, retinal disorders, glaucoma, visual field defects, diplopia, decreased visual acuity, myopia, asthenopia, floating vitreous opacities, iris disorders, mydriasis, halos in the field of vision, eye edema, eye swelling, eye disorders, conjunctival hyperemia, eye irritation, abnormal sensations in the eyes, eyelid edema, sclera discoloration.
On the part of the organs of hearing: infrequently - vertigo, tinnitus; rarely - deafness.
Cardiovascular system: often - flushing, hot flushes; infrequently - tachycardia, palpitations, hypotension/hypertension; rarely - sudden cardiac death*, myocardial infarction, ventricular arrhythmia*, atrial fibrillation, unstable angina.
On the part of the respiratory system: often - nasal congestion; infrequently - nosebleeds, sinus congestion; rarely - a feeling of tightness in the throat, swelling of the nasal mucosa, dry nose.
On the part of the digestive tract: often - nausea, dyspepsia; infrequently - gastroesophageal reflux disease, vomiting, upper abdominal pain, dry mouth; rarely - oral hypoesthesia.
Skin and subcutaneous tissue disorders: uncommon - rash; rare - Stevens-Johnson syndrome*, toxic epidermal necrolysis*.
Musculoskeletal system: infrequently - myalgia, pain in the extremities.
From the urinary system: infrequently - hematuria.
From the reproductive system: rarely - bleeding from the penis, priapism*, hematospermia, prolonged erection.
General disorders: infrequently - chest pain, fatigue, feeling hot; rarely - irritation.
Laboratory indicators: infrequently - increased heart rate.
*Reported only during the study.
** Color perception disorders: chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia.
*** Lacrimation disorders: dry eyes, lacrimation disorders and lacrimation increased.
The following phenomena have been observed in
General disorders: facial edema, photosensitivity reactions, shock, asthenia, pain, sudden fall, abdominal pain, sudden injury.
Cardiovascular system: angina pectoris, AV block, migraine, postural hypotension, myocardial ischemia, cerebral thrombosis, sudden cardiac arrest, ECG abnormalities, cardiomyopathy.
On the part of the digestive tract: 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.
From the respiratory system: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation, increased cough.
Skin: urticaria, herpes, itching, increased sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.
From the sensory organs: sudden decrease or loss of hearing, ear pain, hemorrhage in the eye, cataract, dry eyes.
From the urinary system: cystitis, nocturia, increased frequency of urination, breast enlargement, urinary incontinence, ejaculation disorder, swelling of the genitals, anorgasmia.
Adverse reactions reported from a population of unknown size. These events were listed either because of their seriousness, frequency of reporting, lack of a clear alternative relationship, or a combination of these factors.
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. Most, but not all, patients had pre-existing cardiovascular risk factors. Many of these events have been reported to occur during or shortly after sexual activity and a few have occurred immediately after sildenafil use without sexual activity. Others have occurred in the hours or days following sildenafil use and sexual activity. It is not possible to determine whether these events are related to sildenafil use, sexual activity, pre-existing risk factors, a combination of these factors, or other factors.
Circulatory and lymphatic systems: vaso-occlusive crisis.
In a small, prematurely terminated study of sildenafil in patients with pulmonary arterial hypertension secondary to sickle cell disease, vaso-occlusive crises requiring hospitalization were reported more frequently with sildenafil than with placebo. The clinical relevance of this information for patients using Erosil for the treatment of erectile dysfunction is unknown.
Specific feelings.
Hearing. Cases of sudden hearing loss or hearing impairment have been reported in association with sildenafil use. In some cases, underlying medical conditions and other factors that may have contributed to the development of hearing adverse reactions have been reported. In many cases, follow-up information is not available. It is not possible to determine whether these events are directly related to sildenafil use, to existing risk factors for hearing loss, to a combination of these factors, or to other factors.
Vision: Temporary loss of vision, eye redness, burning in the eyes, increased intraocular pressure, retinal edema, retinal vascular disease or bleeding, vitreous detachment.
Cases of non-arteritic anterior ischemic optic neuropathy, which has been associated with visual impairment, including permanent vision loss, have been reported in association with the use of PDE5 inhibitors, including sildenafil. Many, but not all, patients had anatomic or vascular risk factors for the development of non-arteritic anterior ischemic optic neuropathy, including but not limited to: low optic disc diameter ratio (congestive 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 the use of PDE5 inhibitors or to the underlying anatomic or vascular risk factors.
