Instructions Ergos tablets 50 mg blister No. 2
Composition
active ingredient: sildenafil;
1 tablet contains 50 mg of sildenafil citrate, equivalent to 100% 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 interspersed score lines on one side and the company logo on the other.
Pharmacotherapeutic group
Drugs used for erectile dysfunction.
ATX code G04B E03.
Pharmacological properties
Pharmacodynamics.
Ergos® is an oral medication intended for the treatment of erectile dysfunction. During sexual arousal, the drug restores reduced erectile function by increasing blood flow to the penis.
Ergos® is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).
The physiological mechanism that causes an erection is the release of nitric oxide (NO) in the corpora cavernosa during sexual arousal. The released nitric oxide activates the enzyme guanylate cyclase, which causes an increase in the level of cyclic guanosine monophosphate (cGMP), which in turn causes relaxation of the smooth muscles of the corpora cavernosa and increased blood flow to them.
Sildenafil does not have a direct relaxing effect on the isolated human corpus cavernosum, but enhances the effectiveness of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for the degradation of cGMP in the corpus cavernosum.
When sexual stimulation results in local release of NO, sildenafil inhibition of PDE5 causes an increase in cGMP levels in the corpus cavernosum, resulting in smooth muscle relaxation and increased blood flow to the corpus cavernosum.
The use of sildenafil at recommended doses is ineffective in the absence of sexual stimulation.
In vitro studies have shown that sildenafil is selective for PDE5. Its effect on PDE5 is stronger than that of other known phosphodiesterases (tenfold stronger than PDE6, 80fold stronger than PDE1, 700fold stronger than PDE2, PDE3, PDE4, PDE7-PDE11). In particular, sildenafil has a 400-fold better selectivity for PDE5 than for PDE3, a cGMP-specific isoform of phosphodiesterase involved in the regulation of heart rate.
Efficacy: The efficacy of sildenafil, assessed in terms of the drug's ability to achieve and maintain an erection sufficient for sexual intercourse, has been demonstrated and maintained with long-term use of the drug (1 year).
In the study, sildenafil at doses of 25 mg, 50 mg, or 100 mg improved erections in 62%, 74%, and 82%, respectively. In addition to improving erectile function, analysis of the International Index of Erectile Function (IIEF) showed that sildenafil treatment also increased orgasm and sexual satisfaction.
When treated with sildenafil, improvement was noted in 59% of patients with diabetes mellitus; in patients who underwent radical prostatectomy, 43%; in patients with spinal cord injury, 83%.
Pharmacokinetics.
Within the recommended dose range, sildenafil pharmacokinetics are dose-proportional. The drug is eliminated from the body primarily by hepatic biotransformation (primarily involving cytochrome P450 3A4) to form an active metabolite with properties similar to sildenafil.
Absorption. Sildenafil is rapidly absorbed after oral administration with an absolute bioavailability of 41% (25%-63%). Sildenafil inhibits the PDE5 enzyme in vitro by 50% at a concentration of 3.5 nM. The average plasma concentration after taking sildenafil at a dose of 100 mg is approximately 18 ng/ml or 38 nM. The maximum plasma concentrations observed were recorded 30-120 min (mean 60 min) after oral administration on an empty stomach. In cases where the drug is taken with a high-fat meal, the rate of absorption is reduced, and the delay in Tmax is on average 60 min, and the decrease in Cmax is on average 29%, but the extent of absorption is not impaired (AUC decreased by 11%).
Distribution. The mean volume of distribution of sildenafil at steady state (Vss) is 105 L, indicating tissue penetration. Both sildenafil and its major circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations. In healthy volunteers receiving sildenafil (100 mg once daily), less than 0.0002% of the administered dose (average 188 ng) was detected in ejaculate 90 min after dosing.
Elimination: The total clearance of sildenafil is 41 l/h, with a terminal half-life of 3-5 hours. After oral administration, sildenafil is excreted as metabolites, mainly in the feces (approximately 80% of the administered dose), and to a lesser extent in the urine (approximately 13% of the administered dose).
Pharmacokinetics in special patient groups.
Elderly patients: Healthy elderly volunteers aged 65 years and older had reduced clearance of sildenafil, and concentrations of sildenafil and its N-desmethyl metabolite were approximately 90% higher than in healthy young subjects (18-45 years). Taking into account the age-dependent protein binding, the corresponding increase in free sildenafil plasma concentrations was approximately 40%.
Patients with renal impairment. In volunteers with mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-49 ml/min) renal impairment, the pharmacokinetics of sildenafil were not altered after a single 50 mg oral dose. In volunteers with severe (creatinine clearance < 30 ml/min) renal impairment, sildenafil clearance was reduced, resulting in an increase in AUC (100%) and Cmax (88%) compared to age-matched volunteers with no renal impairment. In addition, the AUC and Cmax values for the N-desmethyl metabolite were significantly increased (200% and 79%, respectively) in patients with severe renal impairment compared to patients with normal renal function.
Patients with hepatic impairment. In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh A and B), sildenafil clearance was reduced, resulting in an increase in AUC (84%) and Cmax (47%), compared to age-matched volunteers without hepatic impairment. The pharmacokinetics of sildenafil in patients with severe hepatic impairment (Child-Pugh C) have not been studied.
Non-clinical data revealed no special hazard for humans based on conventional studies of safety, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.
Indication
Ergos® is recommended for use in men with erectile dysfunction, defined as the inability to achieve and maintain an erection of the penis necessary for successful sexual intercourse. For Ergos® to be effective, sexual arousal is required.
Contraindication
- Concomitant use of Ergos® with nitric oxide donors (such as amylnitrile) or nitrates in any form is contraindicated, as sildenafil is known to affect nitric oxide/cyclic guanosine monophosphate (cGMP) metabolic pathways and potentiate the hypotensive effect of nitrates.
- The drug should not be prescribed to patients for whom sexual activity is undesirable (e.g. patients with unstable angina, with severe heart failure). - Patients with 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 use of Ergos® is contraindicated in persons with increased individual sensitivity to any component of the drug.
- Patients with the following diseases: 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 these subgroups of patients.
Interaction with other medicinal products and other forms of interactions
Effects of other drugs on sildenafil.
In vitro studies: Sildenafil metabolism is mediated primarily by cytochrome P450 (CYP), specifically its isoforms 3A4 (major pathway) and 2C9 (minor pathway). Therefore, inhibitors of these isoenzymes may decrease sildenafil elimination, and inducers of these isoenzymes may increase its elimination.
When a single dose of 100 mg sildenafil was administered with erythromycin, a specific CYP 3A4 inhibitor (500 mg twice daily for 5 days), the systemic exposure (AUC) of sildenafil increased by 182%. Co-administration of the HIV protease inhibitor saquinavir (1200 mg three times daily), also a CYP 3A4 inhibitor, increased sildenafil Cmax by 140% and AUC by 210%. Sildenafil did not affect the pharmacokinetics of saquinavir. Strong CYP 3A4 inhibitors such as ketoconazole and itraconazole may have more pronounced effects. Co-administration of the HIV protease inhibitor ritonavir, which is a highly specific P450 inhibitor, at steady-state (500 mg twice daily) with sildenafil (100 mg once) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1000% (11-fold) increase in sildenafil AUC in plasma. Based on these pharmacokinetic data, co-administration of sildenafil and ritonavir is not recommended. After 24 hours, sildenafil plasma concentrations were approximately 200 ng/ml, compared to 5 ng/ml when sildenafil was administered alone. This is due to ritonavir-mediated effects on P450 isoenzymes. Sildenafil does not affect the pharmacokinetics of ritonavir. When sildenafil was dosed as recommended in subjects receiving a CYP 3A4 inhibitor, plasma sildenafil concentrations did not exceed 200 nM in any patient and the drug was well tolerated. Grapefruit juice is a weak inhibitor of CYP 3A4 in the intestinal wall and may cause modest increases in plasma sildenafil levels.
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.
There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline and dipyrimazole.
Concomitant use of sildenafil and α-adrenergic receptor blockers may lead to symptomatic hypotension in some susceptible patients. This reaction has most often occurred within 4 hours of sildenafil administration (see sections 4.2 and 4.4).
In patients taking sildenafil, no differences in the adverse event profile were observed compared to placebo when concomitantly administered with classes of antihypertensive drugs such as diuretics, α-adrenergic blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive drugs (vasodilators and centrally acting), adrenergic neurone blockers, calcium channel blockers and α-adrenergic blockers.
In healthy male volunteers, steady-state sildenafil (80 mg three times daily) decreased the AUC and Cmax of bosentan (125 mg twice daily) by 49.8% and 42%, respectively.
A single dose of antacid (magnesium hydroxide and aluminum hydroxide) does not affect the bioavailability of sildenafil.
CYP 2C9 inhibitors (such as tolbutamide, warfarin), CYP 2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and related diuretics, angiotensin-converting enzyme inhibitors and calcium channel blockers did not affect the pharmacokinetics of sildenafil.
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. In healthy volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC, Cmax, Tmax, elimination rate and half-life of sildenafil or its major metabolites.
Effects of sildenafil on other drugs.
In vitro studies: sildenafil is a weak inhibitor of cytochrome P450 isoforms, namely 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 > 150 µM). When used in recommended doses, the maximum concentration of sildenafil in blood plasma reaches approximately 1 µM, therefore it is unlikely that sildenafil is able to change the excretion of substrates of these isoenzymes.
In vivo studies: sildenafil enhances the hypotensive effect of short-term and long-term use of nitrates, therefore, single or course use of nitric oxide donors, organic nitrates or organic nitrites in any form with sildenafil is contraindicated.
There was no evidence of a significant interaction between sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg), each of which is metabolized by CYP 2C9.
Sildenafil (100 mg) does not alter the steady-state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, which are CYP 3A4 inhibitors.
Sildenafil (50 mg) does not increase the duration of bleeding caused by acetylsalicylic acid (150 mg).
Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers who had a maximum blood alcohol level of 0.08% (80 mg/dL).
No interaction was observed between sildenafil (100 mg) and amlodipine in patients with hypertension.
The average additional blood pressure reduction was 8 mmHg systolic and 7 mmHg diastolic.
Safety analysis showed no difference in the adverse reaction profile in patients taking sildenafil alone and with antihypertensive drugs.
Application features
To diagnose erectile dysfunction, determine possible causes of the disease and prescribe adequate treatment, it is necessary to carefully study the patient's medical history and conduct medical examinations. Sexual stimulation is necessary for Ergos® to be effective.
Cardiovascular risk factors. Since sexual activity carries a certain cardiac risk, the physician should assess the cardiovascular status of the patient before initiating any treatment for erectile dysfunction. Sildenafil has a vasodilating effect, manifested by a mild and transient decrease in blood pressure (see section "Pharmacological properties"). 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 multisystem 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").
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, which coincided in time with the use of the drug Ergos®. Most, but not all, patients had risk factors for cardiovascular disease. Many of these adverse reactions were observed during or immediately after sexual intercourse and only a few shortly after the use of the drug Ergos® without sexual activity. Therefore, it is not possible to determine whether the development of such adverse reactions is directly related to the risk factors or whether their development is due to other factors.
Priapism: Erectile dysfunction drugs, including sindelafil, should be used with caution in patients with anatomical deformities of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease) or in patients with conditions that may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
Cases of prolonged erection and priapism have been reported in post-marketing experience. In cases where an erection lasts more than 4 hours, patients should seek immediate medical attention. If left untreated, priapism can lead to damage to the penile tissues 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 combinations of sildenafil with other PDE5 inhibitors or other drugs for the treatment of pulmonary arterial hypertension containing sildenafil 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.
Spontaneous reports of visual impairment have been associated with the use of sildenafil and other PDE5 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 PDE5 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).
In patients with age-related retinal degeneration, sildenafil at a dose of 100 mg once daily was well tolerated and had no clinical effect on visual function tests (visual acuity, Amsler grid, color recognition, "artificial light flux", Humphrey perimetry, and photostress).
Some patients with congenital retinitis pigmentosa have been reported to have genetic defects in retinal phosphodiesterase. There is no information on the safety of sildenafil in patients with retinitis pigmentosa, therefore sildenafil should be prescribed with caution in this group of patients.
The simultaneous use of sildenafil and ritonavir is not recommended (see section "Interaction with other medicinal products and other types of interactions").
Concomitant use with α-adrenergic blockers. Sildenafil should be used with caution in patients receiving concomitant α-adrenergic blockers, as in some cases symptomatic hypotension may occur. To minimise the risk of postural hypotension, blood pressure should be stabilised with α-blockers before sildenafil is administered. Sildenafil should be initiated at a low dose. In addition, physicians should advise patients on what to do if symptoms of postural hypotension occur. Symptomatic hypotension usually occurs within 4 hours of sildenafil administration.
Effects on bleeding: In vitro studies with human platelets have shown that sildenafil enhances the anti-aggregatory effect of sodium nitroprusside (an NO donor). There is no safety information regarding the use of sildenafil in patients with a bleeding tendency or with acute gastric ulcer, therefore sildenafil should be used with caution in these patients.
The drug contains lactose, therefore patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome should not use the drug.
After oral administration of a single 100 mg dose of sildenafil, no effect on sperm motility and morphological properties was observed in healthy volunteers.
Hearing loss. Physicians should advise patients to discontinue use of PDE5 inhibitors, including 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 temporal association with the use of PDE5 inhibitors, including Ergos®. 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. Ergos® 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 Ergos® (100 mg) orally 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. The use of ERGOS® does not protect against sexually transmitted diseases. Consideration should be given to instructing patients on the necessary precautions to protect against sexually transmitted diseases, including human immunodeficiency virus.
Use during pregnancy or breastfeeding
The drug ERGOS® is not intended for use in 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 were observed during clinical studies of sildenafil, patients should be aware of their reaction to taking Ergos® before driving or operating machinery.
Method of administration and doses
The drug is administered orally. In each case, the dose of the drug is set individually. Sexual arousal is necessary for the drug to develop its effect. The use of the drug on an empty stomach contributes to the development of an erection on average after 25-30 minutes (12-37 minutes). It is recommended to start taking the drug with a dose of 50 mg. Taking into account the effectiveness and tolerability of the drug, the dose can be increased to 100 mg or reduced to 25 mg. The drug should be used with caution in patients with severe renal failure, patients with arterial hypotension (BP <90/50 mm Hg). The maximum daily dose is 100 mg.
Use in patients with renal impairment. For patients with mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min), the dosage regimen does not change. Since sildenafil clearance is reduced in patients with severe renal insufficiency (creatinine clearance < 30 ml/min), the drug should be started with a dose of 25 mg.
Use in patients with impaired liver function. Since sildenafil clearance is reduced in patients with liver failure, for example, in cirrhosis, the drug should be started at a dose of 25 mg.
Use in elderly patients. No dosage adjustment is required for elderly patients (≥ 65 years).
Children
The drug is not indicated for use in children.
Overdose
In clinical trials involving volunteers, when using a single dose of sildenafil up to 800 mg, adverse reactions were similar to those observed with sildenafil at lower doses, 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, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).
In case of overdose, usual supportive measures should be used 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 safety profile of the drug is based on data from 9570 patients in 74 double-blind, placebo-controlled clinical trials. The most frequently reported adverse reactions were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, cyanopsia and blurred vision. Information on adverse reactions in the post-marketing surveillance was collected over a period of more than 10 years. Since not all adverse reactions were reported, the relationship of the use of PDE5 inhibitors to the occurrence of adverse reactions cannot be reliably determined.
All clinically significant adverse reactions observed in clinical trials at an incidence greater than placebo are listed in the table below by System Organ Class and frequency: very common (≥1/10), common (≥1/100 - <1/10), uncommon (≥1000 - <1/100) and rare (≥1/10000 - <1/1000). 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, hyposthenia.
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, ocular hyperemia, visual acuity reduced, conjunctivitis, photopsia.
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, iris disorders, mydriasis, halos, eye oedema, eye swelling, eye disorders, conjunctival hyperaemia, eye irritation, abnormal sensation in the eyes, eyelid oedema, sclera discolouration.
From the side of the organs of hearing and the vestibular apparatus.
Uncommon: dizziness, tinnitus.
Rare: deafness.
From the heart.
Uncommon: tachycardia, palpitations.
Rare: myocardial infarction, ventricular arrhythmia*, atrial fibrillation, unstable angina.
From the side of the vessels.
Common: hot flashes, 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, dryness in the nose.
From the gastrointestinal tract.
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, pain in extremities.
From the urinary system.
Uncommon: hematuria.
From the reproductive system and mammary glands.
Rare: penile bleeding, priapism*, hematospermia, prolonged erection.
General disorders and administration site reactions.
Uncommon: chest pain, fatigue, feeling hot.
Rare: irritation.
Examination.
Uncommon: increased heart rate.
*- Reported only during post-marketing surveillance.
**- Color perception disorders: chloropsia, cyanopsia, erythropsia, xanthopsia.
***- Lacrimation disorders: dry eyes, lacrimation disorders and increased lacrimation.
The following events occurred in <2% of patients in controlled clinical trials; causality has not been established. 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.
Cardiovascular system: angina pectoris, AV block, migraine, progressive hypotension, myocardial ischemia, cerebral thrombosis, sudden cardiac arrest, ECG abnormalities, cardiomyopathy.
Gastrointestinal disorders: glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, liver function test abnormalities, rectal bleeding, gingivitis.
From the blood and lymphatic system: anemia, leukopenia.
Metabolism and nutrition disorders: thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral phenomena, hyperuricemia, hypoglycemia, hypernatremia.
Musculoskeletal disorders: arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia gravis, synovitis.
Nervous system disorders: ataxia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes.
Respiratory system disorders: asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation, increased cough.
Skin disorders: 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.
Urogenital system disorders: cystitis, nocturia, increased urinary frequency, 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. 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 are listed because of their seriousness, frequency of reporting, and lack of a clear alternative relationship.
Cardiovascular and cerebrovascular events. Serious cardiovascular, cerebrovascular, and vascular events, including cerebrovascular hemorrhage, subarachnoid and intracerebral hemorrhage, and pulmonary hemorrhage, have been reported in temporal association with drug use. Most, but not all, patients had preexisting cardiovascular risk factors. Many of these events have been reported to occur during or immediately after sexual activity. Others have occurred in the hours or days following drug use and sexual activity. It is not possible to determine whether these events are directly related to drug use, sexual activity, preexisting risk factors, or a combination of these factors or other factors.
Blood and lymphatic system: Vaso-occlusive crisis. In a small, prematurely terminated study of 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 significance of this information for patients treated for erectile dysfunction is unknown.
Nervous system: anxiety, transient global amnesia.
Specific feelings.
Hearing. Cases of sudden hearing loss or hearing impairment have been reported in the post-marketing setting, and are thought to be related to the use of the drug. 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. To determine whether these events are directly related to the drug, to existing risk factors for hearing loss, to the combination of
