Instructions Ergos tablets 50 mg blister No. 4
Composition
active ingredient: sildenafil;
1 tablet contains 50 mg of sildenafil;
excipients: lactose monohydrate, magnesium gluconate, powdered sugar, calcium stearate, lemon flavoring, tartrazine dye (E 102).
Dosage form
Pills.
Main physicochemical properties: biconvex yellow tablets with a score line on one side and the company logo on the other.
Pharmacotherapeutic group
Drugs used for erectile dysfunction. Sildenafil. ATX code G04B E03.
Pharmacological properties
Pharmacodynamics
Mechanism of action: Sildenafil is an oral drug 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 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 (PDE-5) in the corpus cavernosum, where PDE-5 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 PDE-5 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 PDE-5, which is actively involved in the process of erection. The effect of sildenafil on PDE-5 is more potent than on other known phosphodiesterases. This effect is 10 times more potent than the effect on PDE-6, which is involved in photoconversion processes in the retina. When using the maximum recommended doses, the selectivity of sildenafil for PDE-5 is 80 times higher than its selectivity for PDE-1, 700 times higher than for PDE-2, PDE-3, PDE-4, PDE-7, PDE-8, PDE-9, PDE-10 and PDE-11. In particular, the selectivity of sildenafil for PDE-5 is 4000 times higher than its selectivity for PDE-3 - 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 plasma 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 delay in time to maximum concentration (Tmax) to 60 minutes and a mean decrease in Cmax by 29%.
Distribution. The average steady-state volume of distribution (Vd) is 105 liters, indicating distribution of the drug into body tissues. After a single oral dose of sildenafil at a dose of 100 mg, the average 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 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 PDE-5 is comparable to that of sildenafil, and the activity of the metabolite for PDE-5 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 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 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), the pharmacokinetics of sildenafil 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 these values in age-matched volunteers without renal impairment. However, due to high individual 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 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
ERGOS® 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 the drug ERGOS® to be effective, sexual arousal is required.
Contraindication
Hypersensitivity to the active substance or to any of the excipients 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 (NO)/cyclic guanosine monophosphate (cGMP) metabolic pathways and potentiate the hypotensive effect of nitrates.
Concomitant use of PDE-5 inhibitors (including sildenafil) with guanylate cyclase stimulators such as riociguat, as this may lead to symptomatic hypotension (see section 4.5).
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, whether or not related to previous use of PDE5 inhibitors.
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), as the safety of sildenafil has not been studied in these 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 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), 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.
Single administration of antacids (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil.
Although specific drug interaction studies with all drugs have not been conducted (based on population pharmacokinetic analysis), sildenafil pharmacokinetics 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 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) with 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 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 NO/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 PDE-5 inhibitors are co-administered with riociguat. Clinical studies have shown that riociguat potentiates the hypotensive effect of PDE-5 inhibitors. No beneficial clinical effect was observed in patients who participated in the study when PDE-5 inhibitors were co-administered with riociguat. Concomitant use of riociguat with PDE-5 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 (see sections 4.4 and 4.2). In 3 specific interaction studies of α-adrenergic blockers, doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg and 100 mg) were administered concomitantly to patients with benign prostatic hyperplasia who were stabilised 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 were observed. Art., 11/4 mm Hg. Art., 4/5 mm Hg. Art., respectively. With the simultaneous use of sildenafil and doxazosin in patients whose condition was stabilized on the use of doxazosin, the development of symptomatic orthostatic hypotension has sometimes been reported. These reports concerned cases of dizziness and presyncope, but without syncope.
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 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, 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.
The addition of a single dose of sildenafil to sacubitril/valsartan at steady state in hypertensive patients was associated with significantly greater reductions in blood pressure compared with sacubitril/valsartan alone. Therefore, caution should be exercised when initiating sildenafil in patients receiving sacubitril/valsartan.
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, which is manifested by a slight 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) 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.
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, hypertension, and hypotension, have been reported in postmarketing experience in patients taking sildenafil. Most, but not all, patients had risk factors for cardiovascular disease. Many of these adverse reactions occurred during or shortly 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 these adverse reactions are directly related to the risk factors or whether they are caused by other factors.
Priapism: Erectile dysfunction drugs, including sildenafil, should be prescribed with caution in patients with anatomical deformity of the penis (angulation, cavernous fibrosis, or Peyronie's disease) or in patients with conditions predisposing to priapism (sickle cell anemia, multiple myeloma, or leukemia).
Cases of prolonged erection and priapism have been reported since sildenafil was marketed. If an erection lasts more 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. Spontaneous reports of visual defects have been reported in association with the use of sildenafil and other PDE-5 inhibitors (see section 4.8). Cases of non-arteritic anterior ischemic optic neuropathy, a rare condition, have been reported spontaneously and in an observational study in association with the use of sildenafil and other PDE-5 inhibitors (see section 4.8). Patients should be advised that in the event of sudden visual impairment, ERGOS® should be discontinued and a physician should be consulted 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 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 section 4.2). Patients should also be advised what to do if they experience symptoms of orthostatic hypotension.
Effects on bleeding. Studies on 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 benefit-risk assessment.
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 ERGOS® 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 association with the use of PDE-5 inhibitors, including ERGOS®. It is not possible to determine whether these events are directly related to the use of PDE-5 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 separate drug interaction study, concomitant use 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 ERGOS® 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.
This medicine contains lactose. Men with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
This medicine contains powdered sugar. If you have been told you have an intolerance to some sugars, contact your doctor before taking this medicine.
The drug contains dye E 102, which may cause allergic reactions when used.
Use during pregnancy or breastfeeding
ERGOS® is not intended for use by women.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect of the drug on the ability to drive and use machines have not been conducted. Since dizziness and visual disturbances have been reported during clinical studies of sildenafil, patients should be advised to assess their individual response to ERGOS® before driving or operating machinery.
Method of administration and doses
The drug is administered orally.
Adults. The recommended dose of ERGOS® is 50 mg, taken as needed 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 in tablets. 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, its effect may occur later than when used on an empty stomach.
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 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 (with the exception of ritonavir, the use of which is not recommended with sildenafil, see sections 4.5 and 4.4), a starting dose of 25 mg should be considered.
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 by persons under the age of 18.
Overdose
In clinical trials involving volunteers, adverse reactions were similar to those observed with sildenafil at lower doses, but were more frequent and more severe. Sildenafil at a dose of 200 mg did not improve efficacy, but increased the incidence 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.
Side effects
The most common adverse reactions reported in clinical trials in patients taking sildenafil were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, hot flushes, visual disturbances, cyanopsia and blurred vision. Information on adverse reactions from post-marketing surveillance of sildenafil has been collected for more than 10 years. All clinically important adverse reactions that occurred in clinical trials with sildenafil at an incidence greater than placebo are listed below, by body system and frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000).
The frequency of clinically important adverse reactions reported from post-marketing experience as unknown is also included.
Within each frequency grouping, side effects are listed in order of decreasing severity.
Infectious and invasive diseases
Uncommon: rhinitis.
On the part of the immune system
Uncommon: hypersensitivity.
From the nervous system
Very common: headache.
Common: dizziness.
Uncommon: drowsiness, hypoesthesia.
Rare: stroke, transient ischemic attack, convulsions*, recurrent convulsions*, 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 eye sensation, 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 vascular side
Common: flushing, hot flushes.
Uncommon: hypertension, hypotension.
Respiratory, thoracic and mediastinal disorders
Common: nasal congestion.
Uncommon: epistaxis, sinus congestion.
Rare: feeling of tightness in the throat, swelling of the nasal mucosa, dry nose.
Gastrointestinal tract
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, pain in extremities.
From the urinary system
Uncommon: hematuria.
Reproductive system and breast disorders
Rare: penile bleeding, priapism*, hematospermia, prolonged erection.
General disorders and administration site conditions
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 were observed in < 2% of patients in controlled clinical trials of sildenafil; causality has not been established. The reports included events that had a probable relationship to drug use. Events that were not listed were mild and the reports were too imprecise to be of significance.
General: 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.
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 disorders: 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, increased 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: Because these reactions are reported voluntarily and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events were reported 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
